PHARMACOLOGICAL COMPARISON OF ANTIPSYCHOTIC-DRUGS AND SIGMA-ANTAGONISTS IN RODENTS

We compared antipsychotic drugs (haloperidol, chlorpromazine and clozapine) and sigma antagonists (remoxipride, cinuperone, alpha-(4-fluorophenyl)-4-2-(fluoro-2-pyrimidinyl)-1-piperzine butanol (BMY 14802) and rimcazole) in the radioligand binding and behavioural experiments in rodents. A good correlation was established between the affinity of compounds at dopamine(2)-receptors in the striatum and their ability to block apomorphine-, amphetamine- and quipazine-induced behavioural effects in rodents. By contrast, no correlation was found between the behavioural effects of these drugs and their affinity at dopamine(1)-, 5-HT2-and sigma receptors. The rank order of potency among the studied antipsychotic drugs in the behavioural tests and at dopamine(2)-receptors was following: haloperidol much greater than chlorpromazine greater than or equal to clozapine. The effectiveness of chlorpromazine and clozapine was nearly similar against apomorphine-induced aggressiveness and yawning, whereas at 5-HT2-receptors clozapine was more active than chlorpromazine. The weak activity of sigma antagonists at dopamine, receptors could be a possible reason why these compounds were less effective in the behavioural studies compared to antipsychotic drugs. However, the antagonism of remoxipride against apomorphine-induced stereotypy and aggressiveness is not related to its activity at sigma receptors, because the other sigma antagonists did nor block these effects of apomorphine. It is probable that remoxipride exerts its action through blocking of dopamine, receptors. In conclusion, the present study revealed only weak activity of sigma antagonists in the behavioural models widely used to study the antipsychotic drugs. Therefore, the antipsychotic activity of sigma antagonists is doubtful.