18-mc for treatment of substance use disorders

Abstract

A composition for treating substance use disorders of an effective amount of 18-Methoxycoronaridine salt (18-MC) in a pharmaceutical carrier. A method of treating substance use disorders, by administering an effective amount of 18-Methoxycoronaridine salt (18-MC) in a pharmaceutical carrier to an individual and preventing substance abuse in the individual. A method of preventing addictive behavior in an individual. A method of preventing craving in an individual. A composition of a metabolite of 18-MC salt. A method of treating substance use disorders by administering an effective amount of a metabolite of 18-MC salt in a pharmaceutical carrier to an individual and preventing substance abuse in the individual. A composition having various pharmacokinetic profiles as shown in the Figures.

What is claimed is: 
     
         1 . A composition for treating substance use disorders comprising an effective amount of 18-Methoxycoronaridine salt (18-MC) in a pharmaceutical carrier. 
     
     
         2 . The composition of  claim 1 , wherein said composition is formulated in an oral dose. 
     
     
         3 . The composition of  claim 1 , wherein said composition is a hydrochloride salt. 
     
     
         4 . A method of treating substance use disorders, including the steps of:
 administering an effective amount of 18-Methoxycoronaridine salt (18-MC) in a pharmaceutical carrier to an individual; and   preventing substance abuse in the individual.   
     
     
         5 . The method of  claim 4 , wherein the substance is chosen from the group consisting of cocaine, nicotine, opiates, alcohol, morphine, and methamphetamine. 
     
     
         6 . The method of  claim 4 , wherein the individual is a human. 
     
     
         7 . The method of  claim 4 , wherein said preventing step is further defined as reducing reinforcing and rewarding effects of the substance. 
     
     
         8 . The method of  claim 4 , wherein said administering step is performed orally. 
     
     
         9 . The method of  claim 4 , wherein the salt is a hydrochloride salt. 
     
     
         10 . The method of  claim 4 , wherein said administering step is further defined as administering 0.01-10 mg/kg of 18-MC. 
     
     
         11 . The method of  claim 10 , wherein said administering step is further defined as administering 20 mg or less per day of 18-MC. 
     
     
         12 . The method of  claim 4 , wherein 18-MC administered follows a multiple-compartment model and a half-life is about 48 hours. 
     
     
         13 . The method of  claim 4 , further including the step of blocking α3β4 nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala. 
     
     
         14 . The method of  claim 4 , further including the step of inhibiting enzymes CYP2C9, CYP2C19, CYP2C8, CYP2E1, and CYP3A4. 
     
     
         15 . A method of preventing addictive behavior in an individual, including the steps of:
 administering an effective amount of 18-Methoxycoronaridine salt (18-MC) in a pharmaceutical carrier to an individual; and   preventing addictive behavior in the individual.   
     
     
         16 . The method of  claim 15 , wherein the salt is a hydrochloride salt. 
     
     
         17 . The method of  claim 15 , wherein the substance is chosen from the group consisting of cocaine, nicotine, opiates, alcohol, morphine, and methamphetamine. 
     
     
         18 . The method of  claim 15 , wherein the individual is a human. 
     
     
         19 . The method of  claim 15 , wherein said preventing step is further defined as reducing reinforcing and rewarding effects of the substance. 
     
     
         20 . The method of  claim 15 , wherein said administering step is performed orally. 
     
     
         21 . The method of  claim 15 , wherein said administering step is further defined as administering 0.01-10 mg/kg of 18-MC. 
     
     
         22 . The method of  claim 21 , wherein said administering step is further defined as administering 20 mg or less per day of 18-MC. 
     
     
         23 . The method of  claim 15 , wherein 18-MC administered follows a multiple-compartment model and a half-life is about 48 hours. 
     
     
         24 . The method of  claim 15 , further including the step of blocking α3β4 nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala. 
     
     
         25 . The method of  claim 15 , further including the step of inhibiting enzymes CYP2C9, CYP2C19, CYP2C8, CYP2E1, and CYP3A4. 
     
     
         26 . A method of preventing craving in an individual, including the steps of:
 administering an effective amount of 18-Methoxycoronaridine salt (18-MC) in a pharmaceutical carrier to an individual; and   preventing craving in the individual.   
     
     
         27 . The method of  claim 26 , wherein the salt is a hydrochloride salt. 
     
     
         28 . The method of  claim 26 , wherein the substance is chosen from the group consisting of cocaine, nicotine, opiates, alcohol, morphine, and methamphetamine. 
     
     
         29 . The method of  claim 26 , wherein the individual is a human. 
     
     
         30 . The method of  claim 26 , wherein said preventing step is further defined as reducing reinforcing and rewarding effects of the substance. 
     
     
         31 . The method of  claim 26 , wherein said administering step is performed orally. 
     
     
         32 . The method of  claim 26 , wherein said administering step is further defined as administering 0.01-10 mg/kg of 18-MC. 
     
     
         33 . The method of  claim 32 , wherein said administering step is further defined as administering 20 mg or less per day of 18-MC. 
     
     
         34 . The method of  claim 26 , wherein 18-MC administered follows a multiple-compartment model and a half-life is about 48 hours. 
     
     
         35 . The method of  claim 26 , further including the step of blocking α3β4 nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala. 
     
     
         36 . The method of  claim 26 , further including the step of inhibiting enzymes CYP2C9, CYP2C19, CYP2C8, CYP2E1, and CYP3A4. 
     
     
         37 . A composition comprising a metabolite of 18-MC salt. 
     
     
         38 . The composition of  claim 37 , wherein said metabolite is chosen from the group consisting of M1, M2, M3, M4, M5, M6, M7, M8, M9, P1, P2, P3, and P10 and wherein the salt is a hydrochloride salt. 
     
     
         39 . The composition of  claim 37 , wherein said metabolite is M4 or M5. 
     
     
         40 . A method of treating substance use disorders including the steps of:
 administering an effective amount of a metabolite of 18-MC salt in a pharmaceutical carrier to an individual; and   preventing substance abuse in the individual.   
     
     
         41 . The method of  claim 40 , wherein the metabolite is chosen from the group consisting of M1, M2, M3, M4, M5, M6, M7, M8, M9, P1, P2, P3, and P10 and wherein the salt is a hydrochloride salt. 
     
     
         42 . The method of  claim 40 , wherein the metabolite is M4 or M5. 
     
     
         43 . The method of  claim 40 , wherein the substance is chosen from the group consisting of cocaine, nicotine, opiates, alcohol, morphine, and methamphetamine. 
     
     
         44 . The method of  claim 40 , wherein the individual is a human. 
     
     
         45 . The method of  claim 40 , wherein said preventing step is further defined as reducing reinforcing and rewarding effects of the substance. 
     
     
         46 . The method of  claim 40 , wherein said administering step is performed orally. 
     
     
         47 . The method of  claim 40 , wherein said administering step is further defined as administering 0.01-10 mg/kg of a metabolite of 18-MC. 
     
     
         48 . The method of  claim 47 , wherein said administering step is further defined as administering 20 mg or less per day of a metabolite of 18-MC. 
     
     
         49 . The method of  claim 40 , wherein a metabolite of 18-MC administered has a half-life of about 48 hours. 
     
     
         50 . The method of  claim 40 , further including the step of blocking α3β4 nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala. 
     
     
         51 . The method of  claim 40 , further including the step of inhibiting enzymes CYP2C9, CYP2C19, CYP2C8, CYP2E1, and CYP3A4. 
     
     
         52 . A composition having the binding profile shown in  FIG.  2   . 
     
     
         53 . A composition having an action potential duration in rabbit cardiac Purkinje fibers shown in  FIG.  13   . 
     
     
         54 . A composition having a pharmacokinetic profiles of parent and a metabolite in human plasma shown in  FIG.  17   . 
     
     
         55 . A composition having an IC 50  profiles of parent and one or more metabolites as shown in  FIG.  18 E . 
     
     
         56 . A composition having an alpha3-beta4 nicotinic cholinergic receptor patch clamp assay profile as shown in  FIGS.  19 A and  19 B . 
     
     
         57 . A composition having a human metabolite alpha3-beta4 nicotinic cholinergic receptor patch clamp assay profile as shown in any of  FIGS.  20 A,  20 B,  20 C and  20 D . 
     
     
         58 . A composition having an ICSS study profile in rats as shown in any of  FIG.  22 ,  23   , or  24 .