Addiction and the potential for therapeutic drug development.
Therapeutic drug development in alcoholism could be targeted at any of the following: direct antagonism, substitution, treatment of abstinence, enhancement of aversion, modification of biodisposition, or craving. Ritanserin is a potent, centrally acting, highly selective 5-HT1C/2 antagonist which, in addition to having a sleep-regulating and anti-depression/anti-axiety effect, displays a unique pharmacological action in several animal paradigms of substance abuse which assess drug-craving. In fact, the latter pharmacological action was demonstrated after initial clinical observations suggested an effect of ritanserin in the chronic withdrawal phase after detoxification from alcohol in patients. The results of a recent double-blind, placebo-controlled, trial indicated that ritanserin did not induce aversion to drink alcohol in normal volunteers who display social drinking, but are not suffering alcohol dependence. Currently, a full clinical development program of ritanserin in cocaine and alcohol abuse is ongoing. Three major double-blind, placebo-controlled trials in alcohol dependent patients are in progress. Patients of different severity levels, ranging from mild to very severe, are studied. The dosages of ritanserin tested (2.5 mg, 5 mg, and 10 mg o.d.) are known to be well tolerated and safe. Two trials aim for relapse prevention--clinically defined in one, biochemically defined in the other-, and one trial has improved (reduced) drinking behaviour as a therapeutic goal. This program, which involves close to 900 alcohol-dependent patients, is well under way, and is still picking up momentum.
Janssen Research Foundation, Beerse, Belgium.
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Janssen
D000437:Alcoholism / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D003042:Cocaine; D004195:Disease Models, Animal; D004311:Double-Blind Method; D006801:Humans; D012107:Research Design; D016713:Ritanserin / Q000627:therapeutic use*; D019966:Substance-Related Disorders / Q000188:drug therapy* / Q000503:physiopathology
D016713:Ritanserin; D003042:Cocaine