The N-type calcium channel is a novel target for treating alcohol use disorders.
We recently validated the N-type calcium channel as a target for the treatment of alcoholism and anxiety. N-type calcium channels are neuronal presynaptic ion channels that regulate neurotransmitter release at many sites in the brain. Mice lacking N-type calcium channels exhibit reduced ethanol consumption and show resistance to the acute intoxicating effects of ethanol. In wild type rodents, pretreatment with a novel N- and T-type calcium channel blocker, NP078585, reduces the intoxicating and reinforcing effects of ethanol and abolishes stress-induced reinstatement of alcohol seeking. Here we discuss these findings and expand upon their implications for the N-type calcium channel as a target for drug development. An important consideration in the development of drugs to treat any addiction is that the medication itself not be addictive. We attempted, and failed, to generate a conditioned place preference for NP078585, suggesting that NP078585 is not rewarding.
Ernest Gallo Clinic and Research Center, Department of Neurology, University of California, San Francisco, Emeryville, CA 94608 , USA.
Philip M
PM
Newton
Robert O
RO
Messing
D019973:Alcohol-Related Disorders / Q000188:drug therapy*; D000818:Animals; D001007:Anxiety / Q000188:drug therapy; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D020864:Calcium Channels, N-Type / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D020318:Rats, Long-Evans; D017211:Treatment Failure; D016896:Treatment Outcome
C534047:1-(6,6-bis(4-fluorophenyl)hexyl)-4-(3,4,5-trimethoxybenzyl)piperazine; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D010879:Piperazines