Abstract:
Although haloperidol is widely prescribed for the treatment of schizophrenia, its beneficial effects are
accompanied by extrapyramidal side effects (EPS). Role of 5-HT-2A/2C receptors in the attenuation of acute
Parkinsonian-like effects of typical antipsychotics is investigated by prior administration of mianserin and
mesulergine to rats injected with haloperidol. In the first part of study effects of various doses of haloperidol
(0.5, 1.0, 2.5 and 5.0 mg/kg) were determined on motor activity and a selected dose (1 mg/kg) was used to
monitor attenuation of parkinsonian effects by two different doses of 5-HT-2A/2C receptor antagonists
mianserin (2.5 & 5.0 mg/kg) and mesulergine (1.0 & 3.0 mg/kg). Rats treated with haloperidol at doses of 0.5-
5.0 mg/kg exhibited impaired motor coordination and a decrease in exploratory activity in an open field. The
dose response curve showed that at a dose of 1 mg/kg significant and submaximal effects are produced on
motor coordination and exploratory activity. Coadministration of mianserin and mesulergine attenuated and
reversed haloperidol-induced motor deficits in a dose dependent manner. The mechanism involved in the
attenuation / reversal of haloperidol-induced parkinsonian like symptoms by mianserin and mesulergine is
discussed. Prior administration of mianserin or mesulergine may be of use in the alleviation of EPS induced by
conventional antipsychotic drugs. The findings have potential implication in the treatment of schizophrenia and
motor disorders.
