Addiction and the potential for therapeutic drug development

EXS. 1994;71:361-70. doi: 10.1007/978-3-0348-7330-7_36.

Abstract

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Review

MeSH terms

  • Alcoholism / drug therapy*
  • Alcoholism / physiopathology
  • Animals
  • Cocaine*
  • Disease Models, Animal
  • Double-Blind Method
  • Humans
  • Research Design
  • Ritanserin / therapeutic use*
  • Substance-Related Disorders / drug therapy*
  • Substance-Related Disorders / physiopathology

Substances

  • Ritanserin
  • Cocaine