Promotion of Smoking Cessation
The present invention relates to a method for promoting cessation or reduction in the smoking and/or chewing of tobacco or nicotine-containing products in a subject in need thereof, comprising administering to the subject an effective amount of certain carbamate compounds. The invention further relates to a method for preventing relapse smoking and/or chewing of tobacco or nicotine-containing products in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of certain carbamate compounds.
1 . A method for promoting cessation or reduction in the smoking and/or chewing of tobacco or nicotine-containing products in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula (I):
or a pharmaceutically acceptable salt or ester thereof;
wherein R is a member selected from the group consisting of alkyl of 1 to 8 carbon atoms, halogen, alkoxy of 1 to 3 carbon atoms, nitro, hydroxy, trifluoromethyl, and thioalkoxy of 1 to 3 carbon atoms;
x is an integer of 0 to 3, with the proviso that R may be the same or different when x is 2 or 3;
R 1 and R 2 are independently selected from the group consisting of hydrogen, alkyl of 1 to 8 carbon atoms, aryl, arylalkyl, cycloalkyl of 3 to 7 carbon atoms; or
R 1 and R 2 can be joined to form a 5 to 7-membered heterocycle that is unsubstituted or substituted with one or more alkyl or aryl groups, wherein the heterocycle can comprise 1 to 2 nitrogen atoms and 0 to 1 oxygen atom, wherein the nitrogen atoms are not directly connected with each other or with the oxygen atom;
wherein the cessation or reduction in the smoking and/or chewing of tobacco or nicotine-containing products is promoted.
2 . A method for preventing relapse smoking and/or chewing of tobacco or nicotine-containing products in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula (I):
or a pharmaceutically acceptable salt or ester thereof;
wherein R is a member selected from the group consisting of alkyl of 1 to 8 carbon atoms, halogen, alkoxy of 1 to 3 carbon atoms, nitro, hydroxy, trifluoromethyl, and thioalkoxy of 1 to 3 carbon atoms;
x is an integer of 0 to 3, with the proviso that R may be the same or different when x is 2 or 3;
R 1 and R 2 are independently selected from the group consisting of hydrogen, alkyl of 1 to 8 carbon atoms, aryl, arylalkyl, cycloalkyl of 3 to 7 carbon atoms; or
R 1 and R 2 can be joined to form a 5 to 7-membered heterocycle that is unsubstituted or substituted with one or more alkyl or aryl groups, wherein the heterocycle can comprise 1 to 2 nitrogen atoms and 0 to 1 oxygen atom, wherein the nitrogen atoms are not directly connected with each other or with the oxygen atom;
wherein relapse smoking and/or chewing of tobacco or nicotine-containing products is prevented.
3 . The method of claim 1 , wherein the subject is not addicted to nicotine.
4 . The method of claim 1 , wherein x=0.
5 . The method of claim 1 , wherein R 1 and R 2 are hydrogen and x=0.
6 . The method of claim 1 , wherein the compound of Formula I is an enantiomer of Formula I substantially free of other enantiomers or an enantiomeric mixture wherein one enantiomer of Formula I predominates.
7 . The method of claim 6 , wherein the enantiomer of Formula I predominates to the extent of about 90% or greater.
8 . The method of claim 6 , wherein the enantiomer of Formula I predominates to the extent of about 98% or greater.
9 . The method of claim 6 , wherein the enantiomer of Formula I is an enantiomer of Formula Ia:
or a pharmaceutically acceptable salt or ester thereof.
10 . The method of claim 9 , wherein the enantiomer of Formula Ia is the (R) or (D) enantiomer.
11 . The method of claim 9 , wherein the enantiomer of Formula Ia is the (S) or (L) enantiomer.
12 . The method of claim 9 , wherein the enantiomer of Formula Ia predominates to the extent of about 90% or greater.
13 . The method of claim 9 , wherein the enantiomer of Formula Ia predominates to the extent of about 98% or greater.
14 . The method of claim 6 , wherein the enantiomer of Formula I substantially free of other enantiomers is the compound of Formula Ib or an enantiomeric mixture wherein the compound of Formula Ib predominates:
or a pharmaceutically acceptable salt or ester thereof.
15 . The method of claim 14 , wherein the compound of Formula Ib predominates to the extent of about 90% or greater.
16 . The method of claim 14 , wherein the compound of Formula Ib predominates to the extent of about 98% or greater.
17 . The method of claim 1 , wherein the effective amount of the compound of Formula I is from about 0.01 mg/kg/dose to about 150 mg/kg/dose.
18 . The method of claim 1 , wherein the effective amount of the compound of Formula I is from about 1 mg/day to about 7000 mg/day.
19 . The method of claim 1 , wherein the compound of Formula I is administered orally.
20 . The method of claim 1 , wherein the compound of Formula I is administered in the form of a capsule or tablet.
21 . The method of claim 1 , wherein the compound of Formula I is administered in the form of a capsule at a dose of about 10 mg to about 1000 mg without any excipients.