5-HT2 antagonism and EPS benefits: is there a causal connection?
This article examines the hypothesis that 5-HT2 antagonism ameliorates extrapyramidal side effects (EPS) induced by the blockade of D2 dopamine receptors by antipsychotics. Neuroanatomical and neurophysiological data confirm the existence of pathways whereby 5-HT2 antagonism may influence EPS. The experimental data in rodents is marginally positive, but shows that the net effect of 5-HT2 antagonism is dependent upon the precise conditions under which catalepsy is induced. The data in monkeys are mainly negative. Studies in patients who have received adjunct 5-HT2 antagonists in addition to typical neuroleptics lend some support the the hypothesis, but are not conclusive. It is reasoned that 5-HT2 antagonism plays no role in clozapine's freedom from EPS, but it may be responsible for risperidone's decreased propensity to cause EPS. The article concludes that there is support for a conditional role of 5-HT2 in decreasing EPS: 5-HT2 antagonists may delay the onset and decrease the severity of EPS but cannot totally eliminate its occurrence. The implications of these findings for the next generation of combined 5-HT2/D2 antagonists are discussed.
Kapur
S
S
PET Centre, Clark Institute of Psychiatry, Toronto, Canada. kapur@clarke-inst.on.ca
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000188:drug therapy*; D003024:Clozapine / Q000494:pharmacology; D006801:Humans; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D018967:Risperidone / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D012702:Serotonin Antagonists; D003024:Clozapine; D018967:Risperidone