Ibogaine Patents @ the USPO

Ibogaine Patents @ the United States Patent Office (USPO)

Use of ibogaine in reducing excitotoxic brain damage
Use of ibogaine in reducing excitotoxic brain damage This invention discloses that ibogaine, a plant derivative, can be used as a safe NMDA antagonist at relatively high dosages (including dosages high enough to cause hallucinations), to reduce or prevent excitotoxic brain damage due to stroke, cardiac arrest, trauma or other forms of neuronal injury or degeneration, without causing the neurotoxic side effects caused by other NMDA antagonist drugs. The relative safety of ibogaine is due to antagonist activity at neuronal sigma receptors, which had not been known prior to discovery by the Applicant. This invention also discloses that ibogaine also can be administered in combination with (1) drugs that suppress activity at muscarinic acetylcholine receptors, or (2) drugs which suppress activity at the kainic acid subclass of glutamate receptors, to reduce or avoid the hallucinatory effects of ibogaine and provide a higher level of neuroprotective activity.
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Method of treating chemical dependency in mammals and a composition therefor
Ibogaine is one of at least 12 alkaloids found in the Tabernanthe iboga shrub of West Africa. The indigenous peoples have used the drug in ritual, ordeal or initiation portions in large dosages and as a stimulant in smaller doses. One of the earliest European references to the drug was made by Professor Baillon on the Mar. 6th, 1889 session of the Linnaen Society in Paris during which he described samples obtained by Griffon de Bellay from Gabon and the French Congo. Early isolation, and identification of ibogaine was accomplished by Dybowski and Landrin (Compt. rend. ac. sc. 133:748, 1901); Haller and Heckel (ibid. 133:850); Lambert and Heckel (ibid. 133:1236) and Landrin (Bull. sc. pharm. 11:1905).
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Rapid method for interrupting or attenuating the nicotine/tobacco dependency syndrome
The administration to a nicotine or tobacco addict of ibogaine, ibogamine or tabernanthine or non-toxic salts of those alkaloids, of the family apocynaceae, has been discovered to interrupt the physiological and psychological aspects of nicotine or tobacco dependency. A single treatment or series of treatments may be effective for one to eighteen months or longer. Treatment consists of the oral, rectal infusion or suppository administration of ibogaine, ibogamine, tabernanthine or their salts in dosage ranges of 1 mg/kg to 60 mg/kg. 2. The method of claim 1 wherein said alkaloid is selected from the group consisting of ibogaine, tabernanthine and ibogamine.
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Bioactive tricyclic ibogaine analogs
Bioactive tricyclic ibogaine analogs Ibogaine analogs are provided, which are phenyl-substituted-hexahydroazepino[4,5-b]indoles useful to treat cocaine addiction and the use of other addictive substances.
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Noribogaine in the treatment of pain and drug addiction
Mash et al, Properties of Ibogaine and its Principle Metabolite (12-hydroxyibogamine) at the MK-801 binding site of the NMDA receptor complex, 1995, Neuroscience Letters, 192, 53-56. cited by examiner . Bagal et al. “Modulation of Morphine-Induced Antinociception by Ibogaine and Noribogaine”, Brain Research, 741: pp. 258-262, 1996. cited by other .
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Methods and compositions for treating addiction disorders
Glick et al., “Effects and Aftereffects of Ibogaine on Morphine Self-administration in Rats,” Europ. J. Pharmacol., 195:341-345 (1991). . Popik et al., “NMDA Antagonist Properties of the Putative Antiaddictive Drug, Ibogaine,” J. Pharmacol. Exp. Ther., 275-753-760 (1995). .
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Ibogamine congeners
Glick et al., “Effects and Aftereffects of Ibogaine on Morphine Self-Administration in Rats,” European Journal of Pharmacology, 195:341-345 (1991). . O’Hearn et al., ” Ibogaine Neurotoxicity Raises New Questions In Addiction Research,” The Journal of NIH Research, 5:50-55 (1993). .
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Formulations and use of controlled-release indole alkaloids
The present invention relates to spray dried hydrophobic phytochemical (i.e., yohimbine and ibogaine) compositions, a process for making such compositions and a method of using such compositions for, e.g., the promotion of weight loss. Typically, the hydrophobic dietary compositions of the present invention exhibit enhanced absorptivity when taken orally. Mash et al., “Medication Development of Ibogaine as a Pharmacotherapy for Drug Dependence,” Annals New York Academy of Sciences 274-292. .
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Preventing neuronal degeneration in Alzheimer’s disease
TABLE 1 COMPARATIVE POTENCIES OF NMDA ANTAGONISTS NMDA ANTAGONIST (AND BINDING SITE) POTENCY RATING (.mu.M) COMPETITIVE (Glutamate Binding Site) CGS 19755 5 CPP 10 D-AP5 25 NON-COMPETITIVE PCP Binding Site MK-801 0.3 Phencyclidine 1 Tiletamine 5 Ketamine 10 Procyclidine 15 Ibogaine 15 Dextromethorphan 25 Polyamine Binding Site Eliprodil 30 Ifenprodil 50 Glycine Binding Site 7-CL-Kynurenic acid 50 CNQX 200 DNQX 100 NBQX 100 Two of the drugs screened by the Applicants using this assay, eliprodil and ibogaine, did not cause this neurotoxic reaction. In addition, a quinoxaline called NBQX also did not cause vacuoles; it was more difficult to handle, because of certain pharmacokinetic properties, so it is described in Example 11, below.
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Method for detecting neuronal degeneration and anionic fluorescein homologue stains therefor
O’Hearn, E. and Molliver, M.E., Degeneration of Purkinje cells in parasagital zones of the cerebellar vermis after treatment with ibogaine or harmaline, Neurosci., 55 (1993) 303-310. . Scallet, A.C., Ye, X., Rountree, R., Nony, P. and Ali, S.F., Ibogaine produces neurodegeneration in rat, but not mouse, cerebellum: Neurohistological biomarkers of Purkinje cell loss, Ann NY Accad. of Sci., in press. .
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Combination for the treatment of alcohol and drug dependence containing an opioid antagonist and a NMDA receptor complex modulator
XP0022092207, E.D. Dzoljic, “Effect of Ibogaine on Naloxone-Precipitated Withdrawal Syndrome in Chronic Morphine-Dependent Rats”, vol. 294, 1988, pp. 64-70 (Abstract). . XP002092209, Susanne Capendijk, “The Inhibitory Effect of Norharman on Morphine Withdrawal Syndrome in Rats: Comparison with Ibogaine”, vol. 65, 1994, pp. 117-119 (Abstract). .
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Modified release formulations of a bupropion salt
Glick, et al., “Effects and aftereffects of ibogaine on morphine self-administration in rats”, Europ. J. Pharmacol., vol. 195, p. 341-345, 1991. cited by other . Popik, et al., “NMDA antagonist properties of the putative antiaddictive drug, ibogaine”, Pharmacology and Experimental Therapeutics, vol. 275, No. 2, p. 753-760, 1995. cited by other .
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Method for treating cocaine and amphetamine dependency
Cocaine and amphetamine abuse has also been treated by administering ibogamine, an alkaloid of the family apocynaceae, and its derivatives to the abuser (U.S. Pat. No. 4,587,243 to Lotsof). However, in humans, as in rats, ibogaine’s efficacy in anti-addictive therapy appears to vary substantially from one individual to another, and at least 30% of treated addicts do not decrease their drug intake. The utility of ibogaine is also limited by several side effects: numbing of the skin; perception of auditory buzzing or oscillating sounds, flashes of light, and the appearance of a vibration to all objects; nausea; and hallucinations. In addition to the stimulant and hallucinogenic side effects, ibogaine induces tremors which appear to be due to activation of an olivo-cerebellar pathway. In rats, high doses of ibogamine have been shown to produce damaged to the cerebellar vermis, presumably a result of overstimulation of cerebellar Purkinje cells.
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Dermal penetration enhancers and drug delivery systems involving same
21. A drug delivery system according to claim 15, wherein the physiologically active agent is testosterone, oestradiol, ethinyloestradiol, progesterone, norethisterone acetate, ibuprofen, ketoprofen, flurbiprofen, naproxen, diclofenac, fentanyl, buprenorphine, scopolamine, prochlorperazine, metochlopramide, ondansetron, tamoxifen, epitiostanol, exemestane, 4-hydroxy-androstenedione and its derivatives, finasteride, turosteride, LY191704, MK-306, alprazolam, alprostadil, prostacylcin and its derivatives, melatonin, n-docosanol, tromantadine, lipophilic pro-drugs of acyclovir, low molecular weight heparin, enoxaparin, sumatriptan, amlodipine, nitrendipine, primaquine, minoxidil, minoxidil pro-drugs, pilocarpine, salbutamol, terbutaline, salmeterol, ibogaine, bupropian, rolipram, tacrine, fluphenazine, haloperidol, N-0923, cyproterone acetate or mazindol. Smoking cessation agents such as nicotine, bupropion and ibogaine.
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Inhibition of serotonin reuptake
Layer, et. al., Structurally modified ibogaine analogs exhibit differing affinities for NMDA receptors, European Journal of Pharmacology, 309, pp. 159-165, 1996. . Repke, et. al., Abbreviated Ibogaine Congeners. Synthesis and Reachtions of Tropan-3-yl-2- and -3-indoles. “Investigation of an Unusual Isomerization of 2-Substituted Indoles Using Computational and Spectroscopic Techniques”, J. of Org. Chem., vol. 59, 1994. .
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Azepino[4,5-b]pyrano[3,2-e]indoles
Mash, D.C., et al., “Identification of a primary metabolite of ibogaine that targets serotonin transporters and elevates serotonin”, Database accession No. 123:47718 Life Sci., 57(3), PL45-PL50, (1995). . Sweetnam, P.M., et al., “Receptor binding profile suggests multiple mechanisms of action are responsiblefor ibogaine’s putative anti-addictive activity”, Chemical Abstracts Service, Columbus, OH, Psychopharmacology (Berlin) 118(4), 369-76, (1995)..
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Determining the effect of a substance on sequestration, uptake, and accumulation of amyloid in brain cells
The invention is also directed to a pharmaceutical composition comprising a compound capable of sufficiently inhibiting the activity of the NMDA receptors in an amount effective to alleviate one or more symptoms of disease states associated with at least one characteristic selected from the group consisting of abnormal accumulation, abnormal molecular organization of amyloid protein and/or amyloid plaques and said composition also includes a suitable carrier or pharmaceutical excipient. Embodiments of the invention may include a composition comprising at least one of the compounds selected from a group consisting of magnesium, ketamine, dextromethorphan, amantadine, dexanabinol, AP3, AP5, AP6, AP7, 4C3HPG, 4CPG, CGS 19755, chlorophenylglutamic acid, CPP, MK-801, PCP, ibogaine, noribogaine, ifenprodil, fiupirtine, selfotel, D-CPP-ene, procyclidine, trihexyphenidyl, CP-101606, CP-98113, GVI150526, AR-R15896AR, NPS 1506, NPC 12626, LY274614, LY 2835959, SDZ 220-040, SDZ 220-040, SDZ 220-581, SDZ 221-653 and memantine. After evaluation the patient is treated with a pharmaceutical composition comprising an appropriate amount of an NMDA antagonist such as magnesium, ketamine, dextromethorphan, amantadine, dexanabinol, AP3, AP5, AP6, AP7, 4C3HPG, 4CPG, CGS 19755, chlorophenylglutamic acid, CPP, MK-801, PCP, ibogaine, noribogaine, ienprodil, flupirtine, selfotel, D-CPP-ene, procyclidine, trihexyphenidyl, CP-101606, CP-
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DNA encoding mammalian neuropeptides FF (NPFF) receptors and uses thereof
TABLE 1 pKi for cloned rat NPFF1 receptor binding in COS-7 cells COMPOUND MEAN SEM n NPFF(F-8-Fa) 8.535 0.02 2 (D-Tyr.sup.1 -(NMe)Phe.sup.3)NPFF 8.549 0.13 4 A18Fa 7.495 0.11 2 PQRFa 8.182 0.03 2 FMRFa 8.481 0.05 2 YFa 8.382 0.22 2 [Y.sup.9 ]A18Fa 7.558 0.12 2 hPP 5.000 0.00 2 fPP 5.500 0.35 2 substance P 5.000 0.00 2 Dynorphin A1-13 6.838 0.29 2 (3D)Y8Fa 8.623 0.44 4 (2D)Y8Fa 8.330 0.15 4 CCK8 5.000 0.00 2 galanin 5.000 0.00 2 dopamine 5.000 0.00 2 naloxone 5.000 0.00 2 CGRP 5.000 0.00 2 AF-1 6.634 0.13 2 AF-2 7.023 0.41 2 SchistFLRF 5.960 0.68 2 Met5-Arg6-Phe7-Enk- 7.350 0.22 4 NH2 Met5-Arg6-Phe7-Enk-OH 5.000 0.00 2 Neuropeptide F 6.110 0.06 4 desamino-nor-Y8Ra 7.270 0.10 3 (2DME)Y8Fa 9.200 0.01 3 L-arginine 5.000 0.00 1 D-arginine 5.000 0.00 1 desipramine 5.000 0.00 1 fenfluramine 5.000 0.00 1 harmine 5.000 0.00 1 levocabastine 5.000 0.00 1 ibogaine 5.000 0.00 1 ritanserine 5.000 0.00 1 a-MSH 5.000 0.00 1 Tyr-MIF-1 5.000 0.00 1 nociceptin 5.000 0.00 1 nocistatin 5.000 0.00 1 PMRFa 8.550 0.06 2 FTRF 7.870 0.10 2 FFRF 8.000 0.001 2 TABLE 2 pKi for rat spinal cord membrane receptor binding COMPOUND MEAN SEM n NPFF(F-8-fa) 9.055 0.08 2 (D-Tyr.sup.1 -(NMe)Phe.sup.3)NPFF *9.724 0.25 4 A18Fa *9.000 0.21 2 PQRFa 8.541 0.07 2 FMRFa 8.493 0.23 2 Y8Fa *9.189 0.06 2 [Y.sup.9 ]A18Fa *8.502 0.01 2 hPP 5.000 0.00 3 fPP *9.118 0.06 3 substance P 5.000 0.00 1 Dynorphin A1-13 *5.700 0.50 2 (3D)Y8Fa 9.123 0.12 4 (2D)Y8Fa *9.212 0.23 4 CCK8 5.000 0.00 2 galanin 5.000 0.00 2 dopamine 5.000 0.00 2 naloxone 5.000 0.00 2 CGRP 5.000 0.00 2 AF-1 *7.563 0.47 2 AF-2 *7.965 0.24 2 SchistFLRF 6.390 0.23 2 Met-Enk-NH2 *8.400 0.08 4 Met-Enk-OH 5.000 0.00 2 Neuropeptide F *8.100 0.10 3 desamino-nor-Y8Ra 7.51 0.07 3 (2DME)Y8Fa 9.570 0.30 4 L-arginine 5.000 0.00 1 D-arginine 5.000 0.00 1 desipiramine 5.000 0.00 1 fenfluramine 5.000 0.00 1 harmine 5.000 0.00 1 levocabastine 5.000 0.00 1 ibogaine 5.000 0.00 1 ritanserine 5.000 0.00 1 a-MSH 5.000 0.00 1 Tyr-MIF-1 5.000 0.00 1 nociceptin 5.000 0.00 1 nocistatin 5.000 0.00 1 PMRFa 9.370 0.11 2 FTRF 8.160 0.16 2 FFRF 8.980 0.001 2 AF-1 = FMRF-like peptide H.sub.2 N-Lys-Asn-Gln-Phe-Ile-Arg-Phe-NH.sub.2 AF-2 H-Lys-His-Gln-Tyr-Leu-Arg-Phe-NH.sub.2 Schisto(FLRFNH.sub.2) = Pro-Asp-Val-Asp-His-Val-Phe-Leu-Arg-Phe-amide Met.sup.5, Arg.sup.6, Phe.sup.7 – NH.sub.2 = enhephalinamide Met.sup.5, Arg.sup.6, Phe.sup.7 – OH = enhephalin
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Cembranoid inhibitors of nicotinic acetylcholine receptors
1. Badio et al., “Ibogaine: a potent noncompetitive blocker of ganglionic/neuronal nicotinic receptors,” Mol. Pharmacol; 51:1-5 (1997).
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Combined use of dopamine and serotonin agonists in the treatment of immune disorders
Ibogaine
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Substituted azepino[4,5b]indole derivatives
Mash, D. C., et al., “Identification of a primary metabolite of ibogaine that targets serotonin transporters and elevates serotonin”, Life Sci., 57(3), CAPLUS Abstract, (1995) 1 page. . Sweetnam, P. M., et al., “Receptor binding profile suggests multiple mechanisms of action are responsible for ibogaine’s putative anti-addictive activity”, Psychopharmacology, vol. 118, (1995), pp. 369-376..
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Bicyclic amine derivatives
Repke, D. B., et al., J. Org. Chem., “Abbreviated Ibogaine Congeners. Synthesis and Reactions of Tropan-3-yl-2-and -3-indoles. Investigation of an Unusual Isomerization of 2-Substituted Indoles Using Computational and Spectroscopic Techniques,” vol. 59, No. 8, 1994, pp. 2164-2171. .
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Method for treating alcohol dependence
Rezvani A H, Overstreet D H, Lee Y W: Attenuation of alcohol drinking by Ibogaine in three strains of alcohol-preferring rats. Pharmacol Biochem Behav. 52:615-620, 1995a.
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Use of flunarizine for the topical treatment of glaucoma
The receptor binding technique was carried out on cell membranes obtained from the irido-ciliary body complex explanted, after sacrifice, from male albino rabbits of the New Zealand strain (Charles River Italiana, of Calco (CO)). The tissue was homogenised in buffer and the P.sub.2, fraction, rich in cell membrane proteins, was isolated. The said fraction was obtained by centrifugation according to what described in the literature (Mach R. H., Smith C. R., Childers S. R. Ibogaine possesses a selective affinity for sigma 2 receptors, Life Sci. 57(4); 5742). The La total protein concentration was determined with the Lowry method.
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Nicotine antagonists for nicotine-responsive neuropsychiatric disorders
“Nicotine Antagonists”, of which mecamylamine is but one example are a large and growing category. A truly exhaustive list of such compounds would take up too much space here. The following discussion is not intended to be exhaustive but to teach how to identify compounds which are encompassed by this term. Currently interesting nicotinic antagonists and related compounds in research were discussed by Daly J W (ibid) which is incorporated by reference. Clark and Reuben (Br. J. Pharmacol. 117: 595-606, 1996) disclose dihydro-beta-erythroidine, methyllycaconitine, chlorisondamine, and trimethaphan. Normecamylamine, N-(1,2,2)trimethyl-1-bicyclo[2,2,1,]-heptylbenzenamine, dimethylaminoisocamphane, exoaminonorbornane, 2,2,6,6-tetramethylpiperdine, 2,2,6,6-tetramethyl4-aminopiperdine, and pempidine were identified as active nicotinic antagonists (Banerjee et al., Biochemical Pharmacology 40: 2105-2110, 1990). This article and its test methods are hereby incorporated by reference. Additional examples of nicotine antagonists include erysodine (Decker, European Journal of Pharmacology 280:79-89, 1995), phenyltropane carboxylic acid methyl esters (Lerner-Marmarosh et al., Life Sciences 56(3): PL 67-70, 1995), arylpempidine analogues (Wang et al., Life Sciences 60(15):1271-1277, 1997); ibogaine (Daly, Biochemical Pharmacology 40(9):2105-10, 1990).
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8-Azabicyclo(3,2,1)oct-2 ene and octane derivatives as cholinergic ligands at nicotinic ACh receptors
J. Med. Chem. 1995, 38, 1998-2008, describes .sigma.-ligands with potential anxiolytic activity. J. Org. Chem. 1994, 59, 2164-2171, describes abbreviated Ibogaine congeners.
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Pyrido-phtalazin diones and their use against neurological disorders associated with excitotoxicity and malfunctioning of glutamatergic neurotransmission
Popik, P., Layer, R.T., Fossom, L.H., Benveniste, M., Geter-Douglass, B., Witkin, J.M., Skolnick, P., Jour. of Pharmacology and Experimental Therapeutics 275 753-760 (1995) “NMDA Antagonist Properties of the Putative Antiaddictive Drug, Ibogaine”. .
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Dha-pharmaceutical agent conjugates to improve tissue selectivity
ibogaine; ibopamine; ibudilast; illimaquinone; ilmofosine; ilomastat; iloperidone; iloprost; imidapril; imidazenil; indinavir; indolidan; indometacin farnesil; indometacin; tropine ester; indoramin; inocoterone; inogatran; inolimomab; interferon alfa; interferon alfa-2a; interferon alfa-2b; interferon alfa-N 1; interferon alfa-n3; interferon beta; interferon beta-1a1; interferon beta-1b; interferon gamma-1a; interferon gamma-1b; interferon omega; interferon, consensus; interleukin-1; interleukin-1 alpha; interleukin- beta; interleukin-10; interleukin-l 1; interleukin-12; interleukin-12; interleukin-15; interleukin-2; interleukin-3; interleukin-4; interleukin-5; interleukin-7; interleukin-8; iobenguane; iobitridol; iodoamiloride; iododoxorubicin; iofratol; iomeprol; iopentol; iopromide; iopyrol; iotriside; ioversol; ioxilan; ipazilide; IpdR; ipenoxazone; ipidacrine; ipomeanol, 4-; ipriflavone; ipsapirone; irbesartan; irinotecan; irloxacin; irsogladine; irtemazole; isalsteine; isbogrel; isepamicin; isobengazole; isofloxythepin; isohomohalicondrin B; isopropyl unoprostone; isradipine; itameline; itasetron; itopride; itraconazole; ketoprofen, R-; ketoprofen, S-; ketorolac; lacidipine; lactitol; lactivicin; laennec; lafutidine; lamellarin-N triacetate; lamifiban; lamivudine; lamotrigine; lanoconazole; lanperisone; lanreotide; lansoprazole; latanoprost; lateritin; laurocapram; lazabemide; lemefloxacin; lemildipine; leminoprazole; lenercept; lenograstim; lentinan sulfate; leptin; leptolstatin; lercanidipine; lerisetron; lesopitron; letrazuril; letrozole; leucomyzin; leuprorelin; levcromakalim; levetiracetam; levobetaxolol; levobunolol; levobupivacaine; levocabastine; levocarnitine; levodropropizine; levofloxacin; levomoprolol; levonorgestrel; levormeloxifene; levosimendan; levosulpiride; linotroban; linsidomine; lintitript; lintopride; liothyronine sodium; lirexapride; lisinopril; lobaplatin; lobucavir; lodoxamide; lombricine; lomefloxacin; lomerizine; lometrexol; lonazolac; lonidamine; loracarbef; loratadine; lorglumide; lomoxicam; losartan; losigamone; losoxantrone; loteprednol; loviride; loxoribine; lubeluzole; lurtotecan; luteinizing hormone; lutetium; luzindole; lydicamycin; lysofylline; lysostaphin; magainin 2 amide; magnolol; mallotochromene; mallotojaponin; malotilate; mangafodipir; manidipine; maniwamycin A; mannostatin A; manumycin E; manumycin F; mapinastine; marimastat; Martek 8708; Martek 92211; masoprocol; maspin; massetolide; meterelin; methoxatone; methylhistamine, R-alpha; methylinosine monophosphate; methylprednisolone aceponate; methylprednisolone suleptanate; metipamide; metoclopramide; metoprolol, S-; metrifonate; mibefradil; michellamine B; microcolin A; midodrine; mifepristone; miglitol; milacemide; milameline; mildronate; milnacipran; milrinone; miltefosine; minaprine; miokamycin; mipragoside; mirfentanil; mirimostim; mirtazapine; misoprostol; mitoguazone; mitolactol; mitonafide; mitoxantrone; mivacurium chloride; mivazerol; mixanpril; mizolastine; mizoribine; moclobemide; modafinil; moexipril; mofarotene; mofezolac; molgramostim; mometasone; montirelin; mopidamol; moracizine; mosapramine; mosapride; motilide; moxiraprine; moxonidine; nadifloxacin; nadroparin calcium; nafadotride; nafamostat; nafarelin; naftopidil; naglivan; nagrestip; nalmefene; naphterpin; napsagatran; naratriptan; nartograstim; nasaruplase; nateplase; niperotidine; niravoline; nisamycin; nisin; nisoldipine; nitazoxanide; nitecapone; nitrendipine; nitrendipine, S-; nitrofurantoin monohydrate; nitrullyn; nizatidine; ofloxacin; okicenone; olanzapine; olopatadine; olprinone; olsalazine; omeprazole; onapristone; ondansetron; ondansetron, R-; ontazolast; oracin; otenzepad; oxaliplatin; oxamisole, oxandrolone; oxaprozin; oxaunomycin; oxcarbazepine; oxiconazole; oxiracetam; oxodipine; ozagrel; palauamine; palinavir; palmitoylrhizoxin; pamaqueside; pamicogrel; pamidronic acid; panamesine; panaxytriol; panipenem; panipenum; pannorin; panomifene; pantethine; pantoprazole; parabactin; pamaparin sodium; paroxetine; parthenolide; pazelliptine; pazufloxacin; pefloxacin; pegaspargase; peldesine; pemedolac; pemirolast; penciclovir; pentafuside; pentamidine; pentamorphone; pentigetide; pentosan; pentostatin; pentrozole; perflubron; perfosfamide; pergolide; perindoprilat; perospirone; phenaridine; phenazinomycin; phenserine; phensuccinal; phentolamine mesilate; phenylacetate; phenylalanyl ketoconazole; picenadol; picibanil; picroliv; picumeterol; pidotimod; pilocarpine hydrochloride; pilsicainide; pimagedine; pimilprost;
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Microparticles
Other biopharmaceutical compounds useful for the practice of the instant invention include but are not limited to sildenafil (Viagra), acyclovir, gancyclovir, fexofenidine, celecoxib (Celebrex), rofecoxib (Vioxx), androstenedione, chloroquine, diphenhydramine HCl, buspirone, doxazocin mesylate, loratadine, clorniphine, zinc gluconate, zinc acetate, hydrocortisone, warfarin, indinavir sulfate, lidocaine, novacaine, estradiol, norethindrone acetate, Medroxyprogesterone, dexfenfluramine, Dextroamphetamine, Doxycycline, thalidomide, fluticasone, fludarabine phosphate, etanercept, metformin hydrochloride, hyaluronate, tetrazocin hydrochloride, loperamide, ibogaine, clonazepam, ketamine, lamivudine (3TC), isotretinoin, nicotine, mefloquine, levofloxacin, atorvastatin (Lipitor), miconazole nitrate (Monistat), ritonavir, famotidine, simvastatin (Zocor), sibutramine HCl monohydride, ofloxacin, lansoprozole, raloxifene (Evista), zanamivir (Relenza), oseltamivir phosphate, 4-phenylbutyric acid sodium salt, chlorpromazine, nevirapine, zidovudine, cetirizine hydrochloride (Zyrtec) and the like.
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Morphine-6-sulfate analogues and their use for the treatment of pain
TABLE 1-4 STANDARDS INHIBITORY EFFECTS (K.sub.i values) OF OPIOIDS ON THE BINDING OF TRITIATED LIGANDS TO .mu.-, .delta.-, AND .kappa.-SITES OF GUINEA-PIG BRAIN HOMOGENATES K.sub.i (nM) .mu. .delta. .kappa..sub.1 .kappa..sub.2 .kappa..sub.3 Cold Ligand [.sup.3 H]DAMGO [.sup.3 H]Cl-DPDPE [.sup.3 H]U69,593 IC.sub.50 (nM) [.sup.3 H]NalBzoH (-) Cyclazocine 0.1 .+-. 0.0 0.6 .+-. 0.05* 0.1 .+-. 0.02 17.3 .+-. 3.0 0.2 .+-. 0 (+) Cyclazocine 659.0 .+-. 28 >10,000* 383.4 .+-. 53 >10,000 785.6 .+-. 121 (-) SKF 10,047-HCl 0.7 .+-. 0.1 3.8 .+-. 0* 0.3 .+-. 0.05 132.5 .+-. 2.0 1.5 .+-. 0.6 (+) SKF 10,047-HCl 2,117.0 .+-. 66 >10,000* 2,889.0 .+-. 140 >10,000 >1,000 (-) Pentazocine- 5.7 .+-. 0.9 32.7 .+-. 3.15* 4.4 .+-. 0.1 423.5 .+-. 171 12.4 .+-. 1.5 succinate (+) Pentazocine- 595.0 .+-. 1.05 3,480.0 .+-. 441* 205.7 .+-. 57 5,270.5 .+-. 1,402 419.8 .+-. 21 succinate NalBzoH 0.2 .+-. 0 1.4 .+-. 0.13 0.4 .+-. 0.1 66.5 .+-. 12 0.3 .+-. 0.07 (-) WIN 44,441 0.1 .+-. 0.03 0.9 .+-. 0.07* 0.2 .+-. 0 6.1 .+-. 0.3 0.3 .+-. 0.05 methane sulfonate .beta.-Endorphin-OH 2.3 .+-. 0.5 1.6 .+-. 0.45* 43.5 .+-. 4.1 2,052.0 .+-. 812 14.5 .+-. 0.4 Ibogaine 3,888.9 .+-. 33 >10,000 4,243.0 .+-. 523 >10,000 1,088.0 .+-. 32 PCP-HCl >10,000 >10,000* >10,000 >10,000 >10,000 TCP-HCl 2,199.0 .+-. 219 >10,000* 2,036.9 .+-. 260 >10,000 >10,000 DTG-OH 1,885.0 .+-. 373 >10,000* 1,033.8 .+-. 264 >10,000 3,487.5 .+-. 279 (+) MK-801-OH >10,000 >10,000* >10,000 >10,000 — (+) 3-PPP-HCl 3,448.4 .+-. 77 >10,000* 388.0 .+-. 110 >10,000 782.1 .+-. 48 *Experiments were done with [.sup.3 H]DPDPE
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Spray on bandage and drug delivery system
Smoking cessation agents such as nicotine, bupropion and ibogaine;
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Method of treating a liver disorder with fatty acid-antiviral agent conjugates
Other pharrnaceutical agents include: 1-decpyrrolidinone; 1-dodecpyrrolidinone; 16-alpha fluoroestradiol; 16-epiestriol; 16alpha-gitoxin; 17alpha estradiol; 17beta estradiol; 1alpha-hydroxyvitamin D2; 2′-nor-cGMP; 20-epi-1,25 dihydroxyvitamin D3; 22-oxacalcitriol; 2CVV; 3-isobutyl GABA; 6-FUDCA; 7-methoxytacrine; abamectin; abanoquil; abecamil; abiraterone; acadesine; acamprosate; acarbose; aceclofenac; acemannan; acetomepregenol; acetyl-L-camitine; acetylcysteine, N-; acetylmethadol; acifran; acipimox; acitemate; acitretin; aclarubicin; aclatonium; napadisilate; aconiazide; acrivastinet; adafenoxate; adapalene; adatanserin; adecypenol; adefovir dipivoxil; adelmidrol; ademetionine; adinazolam; adiposin; adozelesin; adrafinil; alacepril; aladapcin; alaptide; albendazole; albolabrin; aldecalmycin; aldesleukin; alendronic acid; alentemol; alfacalcidol; alfuzosin; alglucerase; alinastine; alosetron; alpha idosone; alprostadil; altretamine; altromycin B; ambamustine; amelometasone; amesergide; amezinium metilsulfate; amfebutamone; amidox; amifloxacin; amifostine; amiodarone; amisulpride; amlexanox; amlodipine; amlodipine; ampiroxicam; amrinone; amrubicin; amsacrine; amylin; amythiamicin; anagrelide; anakinra; ananain; anaritide; anastrozole; andrographolide; anordrin; apadoline; apafant; apaxifylline; aphidicolin glycinate; apraclonidine; aprosulate sodium; aptiganel; apurinic acid; aranidipine; arbekacin; arbidol; arbutamine; ardeparin sodium; arecatannin B1; argatroban; aripiprazol; arotinolol; asimadoline; aspalatone; asperfuran; aspoxicillin; astemizole; asulacrine; atamestane; atenolol, S-; atevirdine; atosiban; atovaquone; atpenin B; atrimustine; atrinositol; aureobasidin A; azadirachtine; azasetron; azatyrosine; azelaic acid; azelastine; azelnidipine; azimilide; azithromycin; azosemide; aztreonam; baccatin III; bacoside A; bacoside B; bactobolamine; balazipone; balhimycin; balofloxacin; balsalazide; bambuterol; baohuoside 1; barnidipine; basifungin; batebulast; batimastat; beauvericin; becaplermin; becliconazole; befloxatone; belfosdil; bellenamine; benflumetol; benidipine; benzisoxazole; benzochlorins; benzoidazoxan; benzoylstaurosporine; benztropine; bepridil; beractant; beraprost; berlafenone; bertosamil; besipirdine; beta-alethine; betaclamycin B; betamipron; betaxolol; betulinic acid; bevantolol; bicalutamide; bifemelane; bimakalim; bimithil; binospirone; bioxalomycin alpha2; biriperone; bis-benzimidazole A; bis-benzimidazole B; bisantrene; bisaramil; bisaziridinylspermine; bisnafide; bisoprolol; bistramide D; bistramide K; bistratene A; boldine; bopindolol; brefeldin; breflate; brimonidine; bromfenac; bromperidol; bropirimine; bucindolol; budesonide; budipine; budotitane; bunaprolast; bunazosin; butenafine; buthionine sulfoximine; butixocort propionate; cadexomer iodine; calanolide A; calcipotriol; calphostin C; camonagrel; candesartan; candesartan cilexetil; candoxatril; candoxatrilat; capecitabine; capromab; capsaicin; captopril; carbazomycin C; carbetocin; carbovir; carboxamide-amino-triazole; carboxyamidotriazole; carboxymethylated beta-1,3-glucan; carperitide; carteolol; carumonam; carvedilol; carvotroline; carzelesin; castanospermine; cebaracetam; cecropin B; cefcapene pivoxil; cefdaloxime pentexil tosilate; cefdinir; cefditoren pivoxil; cefepime; cefetamet; cefetamet pivoxil; cefixime; cefluprenam; cefmetazole; cefminox; cefodizime; cefoselis; cefotetan; cefotiam; cefotiam hexetil; cefozopran; cefpimizole; cefpiramide; cefpirome; cefpodoxime proxetil; cefprozil; cefsulodin; cefteram; ceftibuten; ceftriaxone; cefuroxime axetil; celastrol; celikalim; celiprolol; cepacidine A; cericlamine; cerivastatin; ceronapril; certoparin sodium; cetiedil; cetirizine; chloroorienticin A; chloroorienticin B; chloroquinoxaline sulfonamide; cibenzoline; cicaprost; ciclesonide; cicletanine; cicloprolol; cidofovir; cilansetron; cilazapril; cilnidipine; cilobradine; cilostazol; cimetropium bromide; cinitapride; cinolazepam; cioteronel; ciprofibrate; ciprofloxacin; ciprostene; cis-porphyrin; cisapride; cisatracurium besilate; cistinexine; citalopram; citicoline; citreamicin alpha; cladribine; clarithromycin; clausenamide; clebopride; clinafloxacin; clobazam; clobetasone butyrate; clodronic acid; clomethiazole; clopidogrel; clotrimazole; colestimide; colfosceril palmitate; collismycin A; collismycin B; combretastatin A4; complestatin; conagenin; contignasterol; contortrostatin; cosalane; costatolide; cotinine; coumermycin Al; cucumariosid; curacin A; curdlan sulfate; curiosin; cyclazosin; cyclic HPMPC; cyclobenzaprine; cyclobut A; cyclobut G; cyclocapron; cycloplatam; cyclosin; cyclothialidine; cyclothiazomycin; cypemycin; cyproterone; cytarabine ocfosfate; cytochalasin B; dacliximab; dactimicin; daidzein; daidzin; dalfopristin; dalteparin sodium; danaparoid; daphnodorin A; dapiprazole; dapitant; darifenacin; darlucin A; darsidomine; ddUTP; decitabine; deferiprone; deflazacort; dehydrodidemnin B; dehydroepiandrosterone; delapril; delequamine; delfaprazine; delmopinol; delphinidin; deoxypyridinoline; deprodone; depsidomycin; deramciclane; dermatan sulfate; desflurane; desirudin; deslorelin; desmopressin; desogestrel; desoxoamiodarone; detajmium bitartrate; dexifosfamide; dexketoprofen; dexloxiglumide; dexmedetomidine; dexpemedolac; dexrazoxane; dexsotalol; dextrin 2-sulphate; dexverapamil; dezinamide; dezocine; diaziquone; diclofenac digolil; diclofenac potassium; dicranin; didemnin B; didox; dienogest; diethylhomospermine; diethylnorspermine; dihydrexidine; dihydro-5-azacytidine; dimethyl prostaglandin A1; dimethylhomospermine; dimiracetam; dioxamycin; diphencyprone; diphenyl spiromustine; diprafenone; dipropylnorspermine; dirithromycin; discodermolide; disulfiram; ditekiren; docarpamine; docosanol, 1-; dofetilide; dolasetron; domitroban; dopexamine; dorzolamide; dosmalfale; dotarizine; doxacurium chloride; doxazosin; doxifluridine; doxofylline; draculin; draflazine; droloxifene; dronabinol; drosperidone; drotaverine acephyllinate; droxicam; ebiratide; ebrotidine; ebselen; ecabapide; ecabet; ecadotril; ecdisteron; echicetin; echistatin; ecomustine; ecteinascidin 722; ecteinascidin 729; ecteinascidin 743; edaravone; edelfosine; edobacomab; edrecolomab; efegatran; eflomithine; efonidipine; egualen; elcatonin; eletriptan; elgodipine; eliprodil; eltenac; emakalim; emedastine; emiglitate; emitefur; emoctakin; enadoline hydrochloride; enalapril; enazadrem; englitazone; enlimomab; enoxacin; enoxaparin sodium; enoximone; entacapone; enterostatin; epoprostenol; epoxymexrenone; epristeride; eprosartan; eptastigmine; erdosteine; ersentilide; ersofermin; erythritol; esuprone; etanidazole; etanterol; ethacizin; ethinylestradiol; etizolam; etodolac; etoposide phosphate; etrabamine; everninomicin; examorelin; exemestane; fadrozole; faeriefungin; famciclovir; fampridine; fantofarone; faropenem; fasidotril; fasudil; fazarabine; fedotozine; felbamate; fenofibrate; fenoldopam; fenretinide; fenspiride; fenticonazole; fepradinol; ferpifosate sodium; ferristene; ferrixan; ferumoxsil; fexofenadine; flavopiridol; flecainide; flerobuterol; fleroxacin; flesinoxan; flezelastine; flobufen; flomoxef; florfenicol; florifenine; flosatidil; fluasterone; fluconazole; fludarabine; flumazenil; flumecinol; flumequine; flunarizine; fluocalcitriol; fluorodaunorunicin hydrochloride; fluoxetine, R-; fluoxetine, S-; fluparoxan; flupirtine; flurbiprofen axetil; flurithromycin; fluticasone propionate; flutrimazole; fluvastatin; fluvoxamine; forasartan; forfenimex; formestane; formoterol; formoterol, R,R-; fosfomycin; trometamol; fosinopril; fosphenytoin; fostriecin; fotemustine; gabapentin; gadobenic acid; gadobutrol; gadodiamide; gadodiamide-EOB-DTPA; gadolinium texaphyrin; gadoteric acid; gadoteridol; gadoversetamide; galantamine; galdansetron; gallopamil; galocitabine; gamolenic acid; ganirelix; gepirone; gestrinone; girisopam; glaspimod; glaucocalyxin A; glutapyrone; glycopine; glycopril; granisetron; grepafloxacin; halichondrin B; halofantrine; halomon; halopredone; hatomamicin; hatomarubigin A; hatomarubigin B; hatomarubigin C; hatomarubigin D; ibogaine; ibopamine; ibudilast; illimaquinone; ilmofosine; ilomastat; iloperidone; iloprost; imidapril; imidazenil; indinavir; indolidan; indometacin farnesil; indometacin; tropine ester; indoramin; inocoterone; inogatran; inolimomab; interferon alfa; interferon alfa-2a; interferon alfa-2b; interferon alfa-N 1; interferon alfa-n3; interferon beta; interferon beta-1al; interferon beta-1b; interferon gamma-1a; interferon gamma-1b; interferon omega; interferon, consensus; interleukin-1; interleukin-1 alpha; interleukin-1 beta; interleukin-10; interleukin-11; interleukin-12; interleukin-12; interleukin-15; interleukin-2; interleukin-3; interleukin-4; interleukin-5; interleukin-7; interleukin-8; iobenguane; iobitridol; iodoamiloride; iododoxorubicin; iofratol; iomeprol; iopentol; iopromide; iopyrol; iotriside; ioversol; ioxilan; ipazilide; IpdR; ipenoxazone; ipidacrine; ipomeanol, 4-; ipriflavone; ipsapirone; irbesartan; irinotecan; irloxacin; irsogladine; irtemazole; isalsteine; isbogrel; isepamicin; isobengazole; isofloxythepin; isohomohalicondrin B; isopropyl unoprostone; isradipine; itameline; itasetron; itopride; itraconazole; ketoprofen, R-; ketoprofen, S-; ketorolac; lacidipine; lactitol; lactivicin; laennec; lafutidine; lamellarin-N triacetate; lamifiban; lamivudine; lamotrigine; lanoconazole; lanperisone; lanreotide; lansoprazole; latanoprost; lateritin; laurocapram; lazabemide; lemefloxacin; lemildipine; leminoprazole; lenercept; lenograstim; lentinan sulfate; leptin; leptolstatin; lercanidipine; lerisetron; lesopitron; letrazuril; letrozole; leucomyzin; leuprorelin; levcromakalim; levetiracetam; levobetaxolol; levobunolol; levobupivacaine; levocabastine; levocarnitine; levodropropizine; levofloxacin; levomoprolol; levonorgestrel; levormeloxifene; levosimendan; levosulpiride; linotroban; linsidomine; lintitript; lintopride; liothyronine sodium; lirexapride; lisinopril; lobaplatin; lobucavir; lodoxamide; lombricine; lomefloxacin; lomerizine; lometrexol; lonazolac; lonidamine; loracarbef; loratadine; lorglumide; lomoxicam; losartan; losigamone; losoxantrone; loteprednol; loviride; loxoribine; lubeluzole; lurtotecan; luteinizing hormone; lutetium; luzindole; lydicamycin; lysofylline; lysostaphin; magainin 2 amide; magnolol; mallotochromene; mallotojaponin; malotilate; mangafodipir; manidipine; maniwamycin A; mannostatin A; manumycin E; manumycin F; mapinastine; marimastat; Martek 8708; Martek 92211; masoprocol; maspin; massetolide; meterelin; methoxatone; methylhistamine, R-alpha; methylinosine monophosphate; methylprednisolone aceponate; methylprednisolone suleptanate; metipamide; metoclopramide; metoprolol, S-; metrifonate; mibefradil; michellamine B; microcolin A; midodrine; mifepristone; miglitol; milacemide; milameline; mildronate; milnacipran; milrinone; miltefosine; minaprine; miokamycin; mipragoside; mirfentanil; mirimostim; mirtazapine; misoprostol; mitoguazone; mitolactol; mitonafide; mitoxantrone; mivacurium chloride; mivazerol; mixanpril; mizolastine; mizoribine; moclobemide; modafinil; moexipril; mofarotene; mofezolac; molgramostim; mometasone; montirelin; mopidamol; moracizine; mosapramine; mosapride; motilide; moxiraprine; moxonidine; nadifloxacin; nadroparin calcium; nafadotride; nafamostat; nafarelin; naftopidil; naglivan; nagrestip; nalmefene; naphterpin; napsagatran; naratriptan; nartograstim; nasaruplase; nateplase; niperotidine; niravoline; nisamycin; nisin; nisoldipine; nitazoxanide; nitecapone; nitrendipine; nitrendipine, S-; nitrofurantoin monohydrate; nitrullyn; nizatidine; ofloxacin; okicenone; olanzapine; olopatadine; olprinone; olsalazine; omeprazole; onapristone; ondansetron; ondansetron, R-; ontazolast; oracin; otenzepad; oxaliplatin; oxamisole; oxandrolone; oxaprozin; oxaunomycin; oxcarbazepine; oxiconazole; oxiracetam; oxodipine; ozagrel; palauamine; palinavir; palmitoylrhizoxin; pamaqueside; pamicogrel; pamidronic acid; panamesine; panaxytriol; panipenem; panipenum; pannorin; panomifene; pantethine; pantoprazole; parabactin; pamaparin sodium; paroxetine; parthenolide; pazelliptine; pazufloxacin; pefloxacin; pegaspargase; peldesine; pemedolac; pemirolast; penciclovir; pentafuside; pentamidine; pentamorphone; pentigetide; pentosan; pentostatin; pentrozole; perflubron; perfosfamide; pergolide; perindoprilat; perospirone; phenaridine; phenazinomycin; phenserine; phensuccinal; phentolamine mesilate; phenylacetate; phenylalanyl ketoconazole; picenadol; picibanil; picroliv; picumeterol; pidotimod; pilocarpine hydrochloride; pilsicainide; pimagedine; pimilprost; pimobendan; pinacidil; pinocebrin; pioglitazone; pipecuronium bromide; pirarubicin; piretanide; pirfenidone; piritrexim; pirlindole; pirmagrel; pirmenol; pirodavir; pirodomast; piroxicam cinnamate; propagermanium; propentofylline; propionylcarnitine, L-; propiram; propiram + paracetamol; propiverine; propyl bis-acridone; prostaglandin J2; prostratin; protegrin; protosufloxacin; prulifloxacin; pyrazoloacridine; quazepam; quetiapine; quiflapon; quinagolide; quinapril; quinfamide; quinupristin; raloxifene; raltitrexed; ramatroban; ramipril; ramosetron; ranelic acid; ranitidine bismuth citrate; ranolazine; recainam; regavirumab; relaxin; repirinast; resinferatoxin; reticulon; reviparin sodium; revizinone; ricasetron; ridogrel; rifabutin; rifapentine; rifaximin; rilopirox; riluzole; rimantadine; rimexolone; rimoprogin; riodipine; ripisartan; risedronic acid; rispenzepine; risperidone; ritanserin; ritipenem; ritipenem acoxil; ritolukast; ritonavir; rizatriptan benzoate; rohitukine; rokitamycin; ropinirole; ropivacaine; roquinimex; roxatidine; roxindole; roxithromycin; rubiginone B1; ruboxyl; rufloxacin; rupatidine; ruzadolane; safingol; safironil; saintopin; salbutamol, R-; salmeterol; salmeterol, R-salnacedin; sameridine; sampatrilat; sanfetrinem; saprisartan; sapropterin; saquinavir; SarCNU; sarcophytol A sargramostim; sarpogrelate; saruplase; saterinone; satigrel; satumomab pendetide; selegiline; selenium thiosemicarbazone; sematilide; semduramicin; semotiadil; semustine; sermorelin; sertaconazole; sertindole; sertraline; setiptiline; sevirumab; sevoflurane; sezolamide; silipide; silteplase; simendan; simvastatin; sinitrodil; sinnabidol; sipatrigine; sirolimus; sizofiran; somatomedin B; somatomedin C; somatrem; somatropin; sonermin; sotalol; staurosporine; stavudine; stepronin; stipiamide; stiripentol; stobadine; succibun; sucralfate; sulfasalazine; sulfinosine; sulfoxamine; sulopenem; sultamicillin; sultopride; sulukast; sumatriptan; symakalim; tandospirone; tapgen; taprostene; tasosartan; tazanolast; tazarotene; teicoplanin; telenzepine; tellurapyrylium; telmesteine; telmisartan; temocapril; temoporfin; temozolomide; tenidap; teniposide; tenosal; tenoxicam; tepirindole; tepoxalin; terazosin; terbinafme; terfenadine; terflavoxate; terguride; terlakiren; terlipressin; terodiline; tertatolol; testosterone buciclate; tetrachlorodecaoxide; tetrazomine; thaliblastine; thalidomide; thiocoraline; thiofedrine; thiomarinol; thioperamide; thyroid stimulating hormone; tiagabine; tianeptine; tiapafant; tibolone; ticlopidine; tienoxolol; tilisolol; tilnoprofen arbamel; tiludronic acid; tinzaparin sodium; tiotropium bromide; tipredane; tiqueside; tirandalydigin; tirapazamine; tirilazad; tirofiban; tiropramide; topsentin; torasemide; toremifene; tosufloxacin; trafermin; trandolapril; traxanox; tretinoin; tretinoin tocoferil; triacetyluridine; tricaprilin; trichohyalin; trichosanthin, alpha; triciribine; trientine: triflavin; trimegestone; triptorelin; troglitazone; trombodipine; tropisetron; trospectomycin; trovafloxacin; trovirdine; tucaresol; tulobuterol; tylogenin; urapidil; uridine triphosphate; valaciclovir; valproate magnesium; valproate semisodium; valsartan; vamicamide; vanadeine; vaninolol; vapreotide; variolin B; velaresol; venlafaxine; veramine; verapamil, (S); verdins; veroxan; verteporfin; vesnarinone; vexibinol; vigabatrin; vinbumine citrate; vinbumine resinate: vinconate; vinorelbine; vinpocetine; vinpocetine citrate; vintoperol; vinxaltine; voriconazole; vorozole; voxergolide; xemilofiban; ximoprofen; yangambin; zabicipril; zacopride; zacopride, R-; zafirlukast; zalcitabine; zaleplon; zalospirone; zaltoprofen; zanamivir; zankiren; zanoterone; zatebradine; zatosetron; zenarestat; zeniplatin; zifrosilone; zilascorb; zileuton; zinostatin stimalamer; ziprasidone; zoledronic acid; zolmitriptan; zolpidem; zonisamide; zopiclone; zopiclone, S-; zopolrestat; zotepine.
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Therapeutic compounds
U.S. Pat. No. 5,616,575 relates to tricyclic ibogaine analogs of the following formula. ##STR2##
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Bicyclic amines
Repke, D. B., et al., J. Org. Chem., “Abbreviated Ibogaine Congeners. Synthesis and Reactions of Tropan-3-yl-2- and -3-indoles. Investigation of an Unusual Isomerization of 2-Substituted Indoles Using Computational and Spectroscopic Techniques,” vol. 59, No. 8, 1994, pp. 2164-2171. .
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Hapten-carrier conjugates for use in drug-abuse therapy and methods for preparation of same
Additionally, the therapeutic vaccination approach of the present invention to cocaine addiction is compatible with other therapies currently in use or in clinical trials. In fact, early phase co-therapy is highly desirable because of the time necessary to achieve optimal antibody titers. A number of diverse pharmacological agents would be suitable as co-therapies in preventing cocaine relapse, for example, desipramine, buprenorphine, naloxone, halperidol, chlorproazine, bromocriptine, ibogaine, as well as others that may become relevant.
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Protein kinase C epsilon as modulator of anxiety, alcohol consumption and self-administration of drugs of abuse
Onaivi et al. In vivo ibogaine blockade and in vitro PKC action of cocaine. Annals of NY Acad of Sci. 844:227-224, 1998.* .
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Conantokins
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Hapten-carrier conjugates and uses thereof
Other embodiments of the invention include processes for the production of the compositions of the invention and methods of medical treatment using said compositions. Diverse approaches for the treatment of addiction are suitable as co-therapies in preventing relapse, including psychiatric, social and legal remedies. Pharmacologic agents useful in co-treatment of addiction include desipramine, buprenorphine, naloxone, haloperidol, chlorproazine, bromocriptine, ibogaine, mazindol, antidepressants and others that will be apparent to the ordinarily skilled artisan.
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