WO2000023059A2 - Use of anticonvulsant derivatives for treating alcohol dependency - Google Patents
Use of anticonvulsant derivatives for treating alcohol dependency Download PDFInfo
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- WO2000023059A2 WO2000023059A2 PCT/US1999/023769 US9923769W WO0023059A2 WO 2000023059 A2 WO2000023059 A2 WO 2000023059A2 US 9923769 W US9923769 W US 9923769W WO 0023059 A2 WO0023059 A2 WO 0023059A2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
Definitions
- Rl, R2, R3, R4 and R5 are as defined hereinafter are useful in treating alcohol addiction and abuse.
- X is CH2 or oxygen
- Rl is hydrogen or alkyl
- R2, R3, R4 and R5 are independently hydrogen or lower alkyl and, when X is CH2, R4 and R5 may be alkene groups joined to form a benzene ring and, when X is oxygen, R2 and R3 and/or R4 and R5 together may be a methylenedioxy group of the following formula (II):
- R6 and R7 are the same or different and are hydrogen, lower alkyl or are alkyl and are joined to form a cyclopentyl or cyclohexyl ring.
- Rl in particular is hydrogen or alkyl of about 1 to 4 carbons, such as methyl, ethyl and iso-propyl.
- Alkyl throughout this specification includes straight and branched chain alkyl.
- Alkyl groups for R2, R3, R4, R5, R6 and R7 are of about 1 to 3 carbons and include methyl, ethyl, iso-propyl and n-propyl.
- a particular group of compounds of formula (I) is that wherein X is oxygen and both R2 and R3 and R4 and R5 together are methylenedioxy groups of the formula (II), wherein R6 and R7 are both hydrogen both alkyl or combine to form a spiro cyclopentyl or cyclohexyl ring, in particular where R ⁇ and R7 are both alkyl such as methyl.
- a second group of compounds is that wherein X is CH2 and R4 and R5 are joined to form a benzene ring.
- a third group of compounds of formula (I) is that wherein both R2 and R3 are hydrogen.
- the compounds of formula (I) may be synthesized by the following methods:
- the chlorosulfate of the formula RCH2OSO2CI may then be reacted with an amine of the formula R1NH2 at a temperature of abut 40° to 25° C in a solvent such as methylene chloride or acetonitrile to produce a compound of formula (I).
- a solvent such as methylene chloride or acetonitrile.
- the starting materials of the formula RCH2OH may be obtained commercially or as known in the art.
- starting materials of the formula RCH2OH wherein both R2 and R3 and R4 and R5 are identical and are of the formula (II) may be obtained by the method of R. F. Brady in Carbohydrate Research, Vol. 14, p. 35 to 40 (1970) or by reaction of the trimethylsilyl enol ether of a R6COR7 ketone or aldehyde with fructose at a temperature of about 25° C, in a solvent such a halocarbon, e.g. methylene chloride in the presence of a protic acid such as hydrochloric acid or a Lewis Acid such as zinc chloride.
- the trimethylsilyl enol ether reaction is described by G. L. Larson et al in J. Org. Chem. Volaa 38, No. 22, p. 3935 (1973).
- carboxylic acids and aldehydes of the formulae RCOOH and RCHO may be reduced to compounds of the formula RCH2OH by standard reduction techniques, e.g. reaction with lithium aluminum hydride, sodium borohydride or borane-THF complex in an inert solvent such a diglyme, THF or toluene at a temperature of about 0° to 100° C, e.g. as described by H.O. House in "Modern Synthetic Reactions", 2nd Ed., pages 45 to 144 (1972).
- standard reduction techniques e.g. reaction with lithium aluminum hydride, sodium borohydride or borane-THF complex in an inert solvent such a diglyme, THF or toluene at a temperature of about 0° to 100° C, e.g. as described by H.O. House in "Modern Synthetic Reactions", 2nd Ed., pages 45 to 144 (1972).
- the compounds of formula I may also be made by the process disclosed in 5,387,700, which is incorporated by reference herein.
- the compounds of formula I include the various individual isomers as well as the racemates thereof, e.g., the various alpha and beta attachments, i.e., below and above the plane of the drawing, of R2, R3, R4 and R5 on the 6-membered ring.
- the oxygene of the methylenedioxy group (II) are attached on the same side of the 6- membered ring.
- CIE chronic intermittent ethanol
- CIE in rats appears to be an appropriate model of alcohol dependency in humans. Consequently, compounds that reduce or prevent withdrawal signs in CIE rats would be expected to exert similar effects on withdrawal signs in humans with alcohol dependency.
- the degree of ethanol-induced withdrawal was measured quantitatively by the degree to which the threshold for PTZ-induced seizures was reduced.
- the threshold for seizures was significantly higher than for CIE rats treated with vehicle (P ⁇ 0.05) and was essentially the same as for control rats chronically treated with saline rather than ethanol (The R.W. Johnson Pharmaceutical Research Institute Document ID EDMS-USRA-2321301 :3.0). Therefore, based on the threshold for PTZ-induced seizures as representative of ethanol withdrawal signs, topiramate essentially prevented this specific withdrawal sign in CIE rats.
- a compound of formula (I) may be employed at a daily dosage in the range of about 32 to 512 mg, usually in two divided doses, for an average adult human.
- a unit dose would contain about 16 to 128 mg of the active ingredient.
- one or more sulfamate compounds of formula (I) are intimately admixed with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques, which carrier may take a wide variety of forms depending on the form of preparation desired for administration, e.g., oral, by suppository, or parenteral.
- a pharmaceutical carrier may take a wide variety of forms depending on the form of preparation desired for administration, e.g., oral, by suppository, or parenteral.
- any of the usual pharmaceutical media may be employed.
- suitable carriers and additives include water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents and the like;
- suitable carriers and additives include starches, sugars, diluents, granulating agents, lubricants, binders, disintegrating agents and the like. Because of their ease in administration, tablets and capsules represent the most advantageous oral dosage unit form, in which case solid pharmaceutical carriers are obviously employed. If desired, tablets may be sugar coated or enteric coated by standard techniques. Suppositories may be prepared, in which case cocoa butter could be used as the carrier.
- the carrier will usually comprise sterile water, though other ingredients, for example, for purposes such as aiding solubility or for preservation, may be included. Injectable solutions may also be prepared in which case appropriate stabilizing agents may be employed.
- Topiramate is currently available for oral administration in round tablets containing 25 mg, 100 mg or 200 mg of active agent.
- the tablets contain the following inactive ingredients: lactose hydrous, pregelatinized starch, microcrystalline cellulose, sodium starch glycolate, magnesium stearate, purified water, carnauba wax, hydroxypropyl methylcellulose, titanium dioxide, polyethylene glycol, synthetic iron oxide, and polysorbate 80.
- compositions herein will contain, per dosage unit, e.g., tablet, capsule, powder injection, teaspoonful, suppository and the like from about 25 to about 200 mg of the active ingredient.
Abstract
A method for treating alcohol dependency, addition and abuse comprising administering to a mammal afflicted with such condition a therapeutically effective amount for treating such condition of a compound of formula (I): wherein X is CH2 or oxygen; R1 is hydrogen or alkyl; and R?2, R3, R4 and R5¿ are independently hydrogen or lower alkyl and, when X is CH¿2?, R?4 and R5¿ may be alkene groups joined to form a benzene ring and, when X is oxygen, R?2 and R3¿ and/or R?4 and R5¿ together may be a methylenedioxy group of the following formula (II): wherein R?6 and R7¿ are the same or different and are hydrogen, lower alkyl or are alkyl and are joined to form a cyclopentyl or cyclohexyl ring.
Description
ANTICONVULSANT DERIVATIVES USEFUL IN TREATING ALCOHOL DEPENDENCY, ADDICTION AND ABUSE
BACKGROUND OF THE INVENTION
Compounds of Formula I:
are structurally novel antiepileptic compounds that are highly effective anticonvulsants in animal tests (Maryanoff, B.E, Nortey, S.O., Gardocki, J.F., Shank, R.P. and Dodgson, S.P. J. Med. Chem. 30, 880-887, 1987; Maryanoff, B.E., Costanzo, M.J., Shank, R.P., Schupsky, J.J., Ortegon, M.E., and Vaught J.L. Bioorganic & Medicinal Chemistry Letters 3, 2653-2656, 1993). These compounds are covered by US Patent No.4,513,006. One of these compounds 2,3:4,5-bis-O-(l- methylethylidene)-β-D-fructopyranose sulfamate known as topiramate has been demonstrated in clinical trials of human epilepsy to be effective as adjunctive therapy or as monotherapy in treating simple and complex partial seizures and secondarily generalized seizures (E. FAUGHT, B J. WILDER, R.E. RAMSEY, R.A. REIFE, L D. KRAMER, G.W. PLEDGER, R.M. KARIM et. al., Epilepsia 36 (S4 33, 1995; S.K. SACHDEO, R.C. SACHDEO, R.A. REIFE, P. LIM and G. PLEDGER, Epilepsia 36 £S4) 33, 1995), and is currently marketed for the treatment of simple and complex partial seizure epilepsy with or without secondary generalized seizures in approximately twenty countries including the United States, and applications for regulatory approval are presently pending in several additional countries throughout the world.
Compounds of Formula I were initially found to possess anticonvulsant activity in the traditional maximal electroshock seizure (MES) test in mice (SHANK, R.P., GARDOCKI, J.F., VAUGHT, J.L., DAVIS, C.B., SCHUPSKY, J.J., RAFF A, R.B., DODGSON, S.J., NORTEY, S.O., and MARYANOFF, B.E., Epilepsia 35 450-460, 1994). Subsequent studies revealed that Compounds of Formula I were also highly effective in the MES test in rats. More recently topiramate was found to effectively block seizures in several rodent models of epilepsy (J. NAKAMURA, S. TAMURA,
T. KANDA, A. ISHII, K. ISHIHARA, T. SERIKAWA, J. YAMADA, and M. SASA, Eur. J. Pharmacol. 254 83-89, 1994), and in an animal model of kindled epilepsy (A. WAUQUIER and S. ZHOU, Epilepsy Res. 24, 73-77, 1996).
Preclinical studies on topiramate have revealed previously unrecognized pharmacological properties which suggest that topiramate will be effective in treating alcohol addiction and abuse.
DISCLOSURE OF THE INVENTION
Accordingly, it has been found that compounds of the following formula I:
wherein X is O or CH2, and Rl, R2, R3, R4 and R5 are as defined hereinafter are useful in treating alcohol addiction and abuse.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIEMENTS
The sulfamates of the invention are of the following formula (I):
wherein
X is CH2 or oxygen;
Rl is hydrogen or alkyl; and
R2, R3, R4 and R5 are independently hydrogen or lower alkyl and, when X is CH2, R4 and R5 may be alkene groups joined to form a benzene ring and, when X is oxygen, R2 and R3 and/or R4 and R5 together may be a methylenedioxy group of the following formula (II):
wherein
R6 and R7 are the same or different and are hydrogen, lower alkyl or are alkyl and are joined to form a cyclopentyl or cyclohexyl ring.
Rl in particular is hydrogen or alkyl of about 1 to 4 carbons, such as methyl, ethyl and iso-propyl. Alkyl throughout this specification includes straight and branched chain alkyl. Alkyl groups for R2, R3, R4, R5, R6 and R7 are of about 1 to 3 carbons and include methyl, ethyl, iso-propyl and n-propyl. When X is CH2, R4 and R5 may combine to form a benzene ring fused to the 6-membered X-containing ring, i.e., R4 and R5 are defined by the alkatrienyl group =C-CH=CH-CH=.
A particular group of compounds of formula (I) is that wherein X is oxygen and both R2 and R3 and R4 and R5 together are methylenedioxy groups of the formula (II), wherein R6 and R7 are both hydrogen both alkyl or combine to form a spiro cyclopentyl or cyclohexyl ring, in particular where Rβ and R7 are both alkyl such as methyl. A second group of compounds is that wherein X is CH2 and R4 and R5 are joined to form a benzene ring. A third group of compounds of formula (I) is that wherein both R2 and R3 are hydrogen.
The compounds of formula (I) may be synthesized by the following methods:
(a) Reaction of an alcohol of the formula RCH2OH with a chlorosulfamate of the formula CISO2NH2 or CISO2NHR1 in the presence of a base such as potassium a- butoxide or sodium hydride at a temperature of about -20° to 25° C and in a solvent such as toluene, THF or dimethylformamide wherein R is a moiety of the following formula (III):
(b) Reaction of an alcohol of the formula RCH2OH with sulfurylchloride of the formula SO2CI2 in the presence of a base such as triethylamine or pyridine at a temperature of about -40° to 25° C in a solvent such as diethyl ether or methylene chloride to produce a chlorosulfate of the formula RCH2OSO2CI.
The chlorosulfate of the formula RCH2OSO2CI may then be reacted with an amine of the formula R1NH2 at a temperature of abut 40° to 25° C in a solvent such as methylene chloride or acetonitrile to produce a compound of formula (I). The reaction conditions for (b) are also described by T. Tsuchiya et al. in Tet. Letters, No. 36, p. 3365 to 3368 (1978).
(c) Reaction of the chlorosulfate RCH2OSO2CI with a metal azide such as sodium azide in a solvent such as methylene chloride or acetonitrile yields an azidosulfate of the formula RCH2OSO2N3 as described by M. Hedayatullah in Tet.
Lett. p. 2455-2458 (1975). The azidosulfate is then reduced to a compound of formula (I) wherein Rl is hydrogen by catalytic hydrogenation, e.g. with a noble metal and H2 or by heating with copper metal in a solvent such as methanol.
The starting materials of the formula RCH2OH may be obtained commercially or as known in the art. For example, starting materials of the formula RCH2OH wherein both R2 and R3 and R4 and R5 are identical and are of the formula (II) may be obtained by the method of R. F. Brady in Carbohydrate Research, Vol. 14, p. 35 to 40 (1970) or by reaction of the trimethylsilyl enol ether of a R6COR7 ketone or aldehyde with fructose at a temperature of about 25° C, in a solvent such a halocarbon, e.g. methylene chloride in the presence of a protic acid such as hydrochloric acid or a Lewis Acid such as zinc chloride. The trimethylsilyl enol ether reaction is described by G. L. Larson et al in J. Org. Chem. Volaa 38, No. 22, p. 3935 (1973).
Further, carboxylic acids and aldehydes of the formulae RCOOH and RCHO may be reduced to compounds of the formula RCH2OH by standard reduction techniques, e.g. reaction with lithium aluminum hydride, sodium borohydride or borane-THF complex
in an inert solvent such a diglyme, THF or toluene at a temperature of about 0° to 100° C, e.g. as described by H.O. House in "Modern Synthetic Reactions", 2nd Ed., pages 45 to 144 (1972).
The compounds of formula I: may also be made by the process disclosed in 5,387,700, which is incorporated by reference herein.
The compounds of formula I include the various individual isomers as well as the racemates thereof, e.g., the various alpha and beta attachments, i.e., below and above the plane of the drawing, of R2, R3, R4 and R5 on the 6-membered ring. Preferably, the oxygene of the methylenedioxy group (II) are attached on the same side of the 6- membered ring.
The activity of the compounds of formula I in treating alcohol dependency, addiction and abuse was evidenced in experimental research studies using a rat model of chronic intermittent ethanol (CIE) ingestion to induce alcohol withdrawal signs. Withdrawal from abused substances like ethanol is typified experimentally in rodents by anxiety, aggressive behavior, hyperlocomotion, vocalization, aversion to handling, and seizure susceptibility (E. Majchrowicz E, Psychopharmacologia 43, 245-254,1975). Chronic ethanol with repeated withdrawal in rats leads to a kindling-like condition with persistently heightened withdrawal severity (N. Kokka, D. W. Sapp, A.M. Taylor and R. W. Olsen, Alcohol: Clin Exp Res 11, 525-531, 1993). This experimentally induced condition has been termed the chronic intermittent ethanol (CIE) model of drug dependence. In CIE animals, the hippocampus is in a state of hypoinhibition due to a decrease in the functional properties of GABAA receptors (M. Kang, I. Spigelman, D. W. Sapp and R. W. Olsen, Brain Res 709, 221-228, 1996). These observations suggest a connection between the effects of chronic intermittent ethanol, a reduced threshold to seizures induced by pentylenetetrazol (PTZ), and the inhibitory neurotransmitter GABA. In humans, alcohol dependency is due, in part, to alcohol- induced changes in the state of the brain that result in withdrawal signs and symptoms similar to those observed in CIE rats (REF). Therefore CIE in rats appears to be an appropriate model of alcohol dependency in humans. Consequently, compounds that reduce or prevent withdrawal signs in CIE rats would be expected to exert similar effects on withdrawal signs in humans with alcohol dependency. In the study on topiramate using CIE rats, the degree of ethanol-induced withdrawal was measured
quantitatively by the degree to which the threshold for PTZ-induced seizures was reduced. When topiramate was administered to CIE rats (40 mg/kg, i.p.) 1 hr prior to tail vein injection of PTZ, the threshold for seizures was significantly higher than for CIE rats treated with vehicle (P<0.05) and was essentially the same as for control rats chronically treated with saline rather than ethanol (The R.W. Johnson Pharmaceutical Research Institute Document ID EDMS-USRA-2321301 :3.0). Therefore, based on the threshold for PTZ-induced seizures as representative of ethanol withdrawal signs, topiramate essentially prevented this specific withdrawal sign in CIE rats.
For treating alcohol dependency, addiction and abuse, a compound of formula (I) may be employed at a daily dosage in the range of about 32 to 512 mg, usually in two divided doses, for an average adult human. A unit dose would contain about 16 to 128 mg of the active ingredient.
To prepare the pharmaceutical compositions of this invention, one or more sulfamate compounds of formula (I) are intimately admixed with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques, which carrier may take a wide variety of forms depending on the form of preparation desired for administration, e.g., oral, by suppository, or parenteral. In preparing the compositions in oral dosage form, any of the usual pharmaceutical media may be employed. Thus, for liquid oral preparations, such as for example, suspensions, elixirs and solutions, suitable carriers and additives include water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents and the like; for solid oral preparations such as, for example, powders, capsules and tablets, suitable carriers and additives include starches, sugars, diluents, granulating agents, lubricants, binders, disintegrating agents and the like. Because of their ease in administration, tablets and capsules represent the most advantageous oral dosage unit form, in which case solid pharmaceutical carriers are obviously employed. If desired, tablets may be sugar coated or enteric coated by standard techniques. Suppositories may be prepared, in which case cocoa butter could be used as the carrier. For parenterals, the carrier will usually comprise sterile water, though other ingredients, for example, for purposes such as aiding solubility or for preservation, may be included. Injectable solutions may also be prepared in which case appropriate stabilizing agents may be employed. Topiramate is currently available for oral administration in round tablets containing 25 mg, 100 mg or 200 mg
of active agent. The tablets contain the following inactive ingredients: lactose hydrous, pregelatinized starch, microcrystalline cellulose, sodium starch glycolate, magnesium stearate, purified water, carnauba wax, hydroxypropyl methylcellulose, titanium dioxide, polyethylene glycol, synthetic iron oxide, and polysorbate 80.
The pharmaceutical compositions herein will contain, per dosage unit, e.g., tablet, capsule, powder injection, teaspoonful, suppository and the like from about 25 to about 200 mg of the active ingredient.
Claims
1. A method for in treating alcohol dependency, addiction and abuse comprising administering to a mammal afflicted with such condition a therapeutically effective amount for treating such condition of a compound of the formula I:
wherein
X is CH2 or oxygen;
Rl is hydrogen or alkyl; and
R2, R3, R4 and R5 are independently hydrogen or lower alkyl and, when X is CH2,
R4 and R5 may be alkene groups joined to form a benzene ring and, when X is oxygen, R2 and R3 and/or R4 and R5 together may be a methylenedioxy group of the following formula (II):
wherein
R6 and R7 are the same or different and are hydrogen, lower alkyl or are alkyl and are joined to form a cyclopentyl or cyclohexyl ring.
2. The method of claim 1 wherein the compound of formula I is topiramate.
3. The method of claim 1, wherein the therapeutically effective amount is of from about 32 to 512 mg.
4. The method of claim 1, wherein the amount is of from about 16 to 128 mg.
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| MXPA01004015A MXPA01004015A (en) | 1998-10-20 | 1999-10-18 | Anticonvulsant derivatives useful in treating alcohol dependency, addiction and abuse. |
| BR9914722-0A BR9914722A (en) | 1998-10-20 | 1999-10-18 | Anticonvulsant derivatives useful in the treatment of alcohol dependence, addiction and abuse |
| NZ511173A NZ511173A (en) | 1998-10-20 | 1999-10-18 | Method for treating alcohol dependency, addiction and abuse using anticonvulsant derivatives (such as 2,3:4,5-bis- O-(1-methylethylidene)-beta-D-fructopyranose sulfamate (topiramate)) |
| CA002348017A CA2348017C (en) | 1998-10-20 | 1999-10-18 | Anticonvulsant derivatives useful in treating alcohol dependency, addiction and abuse |
| AU13131/00A AU759756B2 (en) | 1998-10-20 | 1999-10-18 | Anticonvulsant derivatives useful in treating alcohol dependency, addiction and abuse |
| JP2000576834A JP2002527470A (en) | 1998-10-20 | 1999-10-18 | Anticonvulsant derivatives useful in the treatment of alcoholism, addiction and abuse |
| NO20011901A NO20011901L (en) | 1998-10-20 | 2001-04-18 | Anti-convulsive derivatives useful in the treatment of alcohol dependence and abuse |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10488798P | 1998-10-20 | 1998-10-20 | |
| US60/104,887 | 1998-10-20 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2000023059A2 true WO2000023059A2 (en) | 2000-04-27 |
| WO2000023059A3 WO2000023059A3 (en) | 2000-11-23 |
Family
ID=22302937
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1999/023769 WO2000023059A2 (en) | 1998-10-20 | 1999-10-18 | Use of anticonvulsant derivatives for treating alcohol dependency |
Country Status (9)
| Country | Link |
|---|---|
| JP (1) | JP2002527470A (en) |
| AU (1) | AU759756B2 (en) |
| BR (1) | BR9914722A (en) |
| CA (1) | CA2348017C (en) |
| MX (1) | MXPA01004015A (en) |
| NO (1) | NO20011901L (en) |
| NZ (1) | NZ511173A (en) |
| WO (1) | WO2000023059A2 (en) |
| ZA (1) | ZA200104037B (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000050020A2 (en) * | 1999-02-24 | 2000-08-31 | University Of Cincinnati | Use of sulfamate derivatives for treating impulse control disorders |
| US6323239B1 (en) | 1998-08-05 | 2001-11-27 | Brookhaven Science Associates | Treatment of addiction to ethanol and addictive-related behavior |
| WO2002043731A3 (en) * | 2000-11-30 | 2003-02-20 | Univ Florida | Treatments for neurogenetic disorders, impulse control disorders, and wound healing |
| EP1392273A1 (en) * | 2001-05-14 | 2004-03-03 | Brookhaven Science Associates | Novel treatment for obsessive-compulsive disorder (ocd) and ocd-related disorders using gvg |
| US6890951B2 (en) | 1998-08-05 | 2005-05-10 | Brookhaven Science Associates Llc | Treatment of addiction and addiction-related behavior |
| US8652527B1 (en) | 2013-03-13 | 2014-02-18 | Upsher-Smith Laboratories, Inc | Extended-release topiramate capsules |
| US9101545B2 (en) | 2013-03-15 | 2015-08-11 | Upsher-Smith Laboratories, Inc. | Extended-release topiramate capsules |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000007583A2 (en) * | 1998-08-05 | 2000-02-17 | Brookhaven Science Associates | Treatment of addiction and addiction-related behavior |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4513006A (en) * | 1983-09-26 | 1985-04-23 | Mcneil Lab., Inc. | Anticonvulsant sulfamate derivatives |
-
1999
- 1999-10-18 MX MXPA01004015A patent/MXPA01004015A/en not_active Application Discontinuation
- 1999-10-18 AU AU13131/00A patent/AU759756B2/en not_active Ceased
- 1999-10-18 JP JP2000576834A patent/JP2002527470A/en active Pending
- 1999-10-18 BR BR9914722-0A patent/BR9914722A/en not_active Application Discontinuation
- 1999-10-18 WO PCT/US1999/023769 patent/WO2000023059A2/en active IP Right Grant
- 1999-10-18 NZ NZ511173A patent/NZ511173A/en unknown
- 1999-10-18 CA CA002348017A patent/CA2348017C/en not_active Expired - Fee Related
-
2001
- 2001-04-18 NO NO20011901A patent/NO20011901L/en not_active Application Discontinuation
- 2001-05-17 ZA ZA200104037A patent/ZA200104037B/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000007583A2 (en) * | 1998-08-05 | 2000-02-17 | Brookhaven Science Associates | Treatment of addiction and addiction-related behavior |
Non-Patent Citations (4)
| Title |
|---|
| D.A. GORELICK: "Pharmacological treatment" RECENT DEVELOPMENTS IN ALCOHOLISM, vol. 11, 1993, pages 413-427, XP000913482 * |
| KYOWA HAKKO: "TOPIRAMATE" DRUGS OF THE FUTURE,ES,BARCELONA, vol. 21, no. 4, 1 January 1996 (1996-01-01), pages 463-465, XP002043895 ISSN: 0377-8282 * |
| T.I. MIELLER: "A double-blind, placebo-controlled pilot study of carbamazepine for the treatment of alcohol dependence" ALCOHOLISM. CLIN. EXP. RES., vol. 21, no. 1, 1997, pages 86-92, XP000913485 * |
| WAUQUIER A ET AL: "TOPIRAMATE: A POTENT ANTICONVULSANT IN THE AMYGDALA-KINDLED RAT" EPILEPSY RESEARCH,NL,ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, vol. 24, no. 2, 1 June 1996 (1996-06-01), pages 73-77, XP002042953 ISSN: 0920-1211 * |
Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6890951B2 (en) | 1998-08-05 | 2005-05-10 | Brookhaven Science Associates Llc | Treatment of addiction and addiction-related behavior |
| US6323239B1 (en) | 1998-08-05 | 2001-11-27 | Brookhaven Science Associates | Treatment of addiction to ethanol and addictive-related behavior |
| US6906099B2 (en) | 1998-08-05 | 2005-06-14 | Brookhaven Science Associates, Llc | Treatment of addiction and addiction-related behavior using a composition of topiramate |
| WO2000050020A3 (en) * | 1999-02-24 | 2000-12-21 | Univ Cincinnati | Use of sulfamate derivatives for treating impulse control disorders |
| US6323236B2 (en) | 1999-02-24 | 2001-11-27 | University Of Cincinnati | Use of sulfamate derivatives for treating impulse control disorders |
| WO2000050020A2 (en) * | 1999-02-24 | 2000-08-31 | University Of Cincinnati | Use of sulfamate derivatives for treating impulse control disorders |
| WO2002043731A3 (en) * | 2000-11-30 | 2003-02-20 | Univ Florida | Treatments for neurogenetic disorders, impulse control disorders, and wound healing |
| US8084491B2 (en) | 2000-11-30 | 2011-12-27 | Novodermix International Limited | Treatments for wound healing |
| EP1392273A4 (en) * | 2001-05-14 | 2004-11-24 | Brookhaven Science Ass Llc | Novel treatment for obsessive-compulsive disorder (ocd) and ocd-related disorders using gvg |
| EP1392273A1 (en) * | 2001-05-14 | 2004-03-03 | Brookhaven Science Associates | Novel treatment for obsessive-compulsive disorder (ocd) and ocd-related disorders using gvg |
| US8652527B1 (en) | 2013-03-13 | 2014-02-18 | Upsher-Smith Laboratories, Inc | Extended-release topiramate capsules |
| US8889190B2 (en) | 2013-03-13 | 2014-11-18 | Upsher-Smith Laboratories, Inc. | Extended-release topiramate capsules |
| US10363224B2 (en) | 2013-03-13 | 2019-07-30 | Upsher-Smith Laboratories, Llc | Extended-release topiramate capsules |
| US9101545B2 (en) | 2013-03-15 | 2015-08-11 | Upsher-Smith Laboratories, Inc. | Extended-release topiramate capsules |
| US9555005B2 (en) | 2013-03-15 | 2017-01-31 | Upsher-Smith Laboratories, Inc. | Extended-release topiramate capsules |
| US10172878B2 (en) | 2013-03-15 | 2019-01-08 | Upsher-Smith Laboratories, Llc | Extended-release topiramate capsules |
Also Published As
| Publication number | Publication date |
|---|---|
| NZ511173A (en) | 2003-09-26 |
| AU1313100A (en) | 2000-05-08 |
| AU759756B2 (en) | 2003-05-01 |
| ZA200104037B (en) | 2002-06-28 |
| CA2348017A1 (en) | 2000-04-27 |
| BR9914722A (en) | 2001-07-10 |
| NO20011901D0 (en) | 2001-04-18 |
| JP2002527470A (en) | 2002-08-27 |
| CA2348017C (en) | 2005-07-19 |
| MXPA01004015A (en) | 2003-03-10 |
| WO2000023059A3 (en) | 2000-11-23 |
| NO20011901L (en) | 2001-04-18 |
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