Ritanserin and alcohol abuse and dependence.

Ritanserin is a potent long-acting 5-HT2 antagonist that acts centrally. In humans, ritanserin increases deep slow wave sleep, improved liveliness in a variety of psychiatric disorders and facilitated participation in behaviour therapy. During clinical trials unexpected observations indicated that ritanserin may be of value in treating drug addicts. Furthermore, initial clinical observations confirmed the efficacy of ritanserin in the chronic withdrawal phase after detoxification from ethanol. In the present paper, four experiments which support the potential of ritanserin as a pharmacological treatment for alcohol abuse and dependence are described. Firstly, ritanserin has been demonstrated to lack abuse potential and any direct interaction with ethanol. Secondly, in various models ritanserin has been shown to reduce alcohol intake and preference. The level of activity varies to some degree depending on the test and treatment procedure, as well as on the animal strain used. Long term ritanserin-related efficacy was illustrated by the gradual increase in alcohol drinking after cessation of the ritanserin treatment. Thirdly, the dopaminergic pathway and the nucleus accumbens have been shown to play a role in the effects of ritanserin. Finally, ritanserin reduces some alcohol withdrawal signs. Based on these findings, a clinical development plan started. After safety-interactions studies, ritanserin was demonstrated to influence the desire to drink in normal volunteers who display heavy social drinking. Currently, three major trials in 900 alcohol-dependent patients with different levels of dependence are running.