neramexane and Alcoholism

In the past two decades, the search for novel pharmacotherapies to treat alcohol addiction has been a global endeavor. This has resulted in several drugs that have been approved and successfully marketed for public use while some are still in the testing phase. These pharmacological agents, though effective for the treatment of alcoholism, are not without shortcomings; such as abuse potential, serious mental and physical adverse effects, interaction with alcohol and also poor metabolism and excretion. As more is being understood about the neurobiology of alcohol addiction as well as the unique pharmacological action of these drugs, new agents are evaluated for potential benefits when used as an adjunct in combination therapy. This review article summarizes the novel pharmacotherapeutic approaches used in the treatment of alcohol addiction by focusing on the drugs, which include neramexane, gabapentin, baclofen, aripiprazole, nalmafene, and quetiapine.

Topics: Alcohol Deterrents; Alcoholism; Animals; Aripiprazole; Baclofen; Cyclopentanes; Gabapentin; Humans; Naltrexone; Quetiapine Fumarate

Topics: Alcoholism; Animals; Cyclopentanes; Humans; Neuroprotective Agents; Pain; Receptors, N-Methyl-D-Aspartate

Effects of acamprosate and ionotropic uncompetitive N-methyl-D-aspartate receptor antagonists and group I metabotropic glutamatergic receptor antagonists on the expression of ethanol-induced sensitization were investigated in mice. The results indicated that acamprosate (200 and 400 mg/kg) and N-methyl-D-aspartate receptor antagonists, neramexane (10 and 20 mg/kg) and MK-801 (0.1 and 0.2 mg/kg), inhibited the expression of ethanol-induced sensitization. Acamprosate, but not the other compounds tested, also blocked the stimulant effect of acute injections of ethanol. Among the group I metabotropic glutamatergic receptor antagonists, only the metabotropic glutamatergic receptor 5 antagonist, MTEP (5, 10, and 20 mg/kg) showed an effect similar to the N-methyl-D-aspartate receptor antagonists. The metabotropic glutamatergic receptor 1 antagonist, EMQMCM (5, 10, and 20 mg/kg), however, potentiated the inhibitory effect of MK-801 on the expression of ethanol-induced sensitization. The findings indicate that glutamatergic neurotransmission is important in the ethanol-induced sensitization process, and suggest that co-administration of metabotropic glutamatergic receptor 1 antagonists and N-methyl-D-aspartate receptor antagonists may be useful in therapy for alcoholism.

Topics: Acamprosate; Alcoholism; Animals; Brain; Cyclopentanes; Dizocilpine Maleate; Dose-Response Relationship, Drug; Drug Synergism; Ethanol; Glutamic Acid; Male; Mice; Motor Activity; N-Methylaspartate; Pyridines; Quinolines; Receptors, Metabotropic Glutamate; Receptors, N-Methyl-D-Aspartate; Stereotyped Behavior; Synaptic Transmission; Taurine; Thiazoles

It has been suggested that drugs modulating the glutamate/N-methyl-D-aspartate (NMDA) receptor system may be useful in the treatment of alcohol dependence. The effect of neramexane, a low-to-moderate affinity uncompetitive NMDA receptor antagonist, was examined on the development and expression of ethanol dependence (withdrawal-associated audiogenic seizures) and ethanol-induced conditioned place preference. Neramexane hydrochloride (3.5 mg/kg and higher) inhibited both the development and expression of ethanol dependence. Neramexane hydrochloride also inhibited the acquisition (1.75 mg/kg and higher) and expression (3.5 mg/kg and higher) of ethanol-induced place preference. Our data support therapeutic potential of neramexane as a treatment for alcohol abuse.

Topics: Acamprosate; Alcohol Deterrents; Alcoholism; Animals; Behavior, Animal; Central Nervous System Depressants; Conditioning, Operant; Cyclopentanes; Ethanol; Male; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Reinforcement, Psychology; Seizures; Substance Withdrawal Syndrome; Taurine