Appearance of Extrapyramidal Symptoms: Interaction between Neuroleptics and Other CNS Active Drugs

Abstract

Neuroleptics were able to induce motor incoordination when administered to rats in large amounts. It has been observed that this effect could be antagonized by some CNS active drugs endowed with dopaminergic stimulants, anticholinergic and antihistaminic properties (such as amphetamine, apomorphine, atropine and diphenhydramine), only when evoked by neuroleptics (haloperidol, metoclopramide and LR 511) causing muscle rigidity. Other antihistaminics blocking H i receptors (chlorpheniramine, chlorcyclizine, cyclizine and promethazine), but not those blocking H₂ receptors (cimetidine), were also effective at least on haloperidol-induced incoordination. On the other hand, specific central antiserotoninergic drugs (metergoline and methysergide) and a peripheral anticholinergic agent (isopropamide) did not antagonize but in some cases potentiated haloperidol and LR 511. Chlorpromazine, clozapine and diazepam (a minor tranquilizer), causing motor incoordination only at doses which strongly relaxed the skeletal muscles, were generally not influenced, or at the most slightly potentiated, by any of the above-mentioned drugs. The incoordination induced by pilocarpine (a direct stimulator of the cholinergic receptors of the extrapyramidal system) was selectively inhibited by drugs possessing antimuscarinic properties (such as atropine and cyproheptadine). Thus, the present results indicate that along with the dopaminergic and cholinergic systems, the histaminergic system also plays an important role in modulating the extrapyramidal activity of hypertonic neuroleptics (revealed in rats by the locomotor incoordination) while, in disagreement with some data of the literature, the serotoninergic system should not have any significance.

Prevention by (±)‐8‐hydroxy‐2‐(di‐npropylamino)tetralin of both catalepsy and the rises in rat striatal dopamine metabolism caused by haloperidol

“…treatment with the 5-HT antagonist, methysergide. Conversely, other studies have reported that catalepsy was unaffected by the 5-HT antagonists, metergoline and methysergide, or by depletion of 5-HT with p-chlorophenylalanine (see, for example, Sarnek & Baran, 1975;Fregnan & Vidali, 1982).…”

Mirtazapine enhances the effect of haloperidol on apomorphine-induced climbing behaviour in mice and attenuates haloperidol-induced catalepsy in rats

“…For instance, in some studies, a reduction of haloperidol-induced catalepsy was found after destruction of serotonergic neurons in the midbrain raphe or by depletion of central 5-HT stores with p-chlorophenylalanine and by blockade of 5-HT receptors with methysergide (Kostowski et al 1972;Carter and Pycock 1977;Balsara et al 1979). In other studies, haloperidol-induced catalepsy was found to be una¤ected after brain 5-HT depletion with p-chlorophenylalanine or by blockade of the 5-HT receptors with metergoline and methysergide (Sarnek and Baran 1975;Fregnan and Vidali 1982;Broekkamp et al 1988). After treatment with the 5-HT agonists quipazine and 5-methoxy-dimethyltryptamine and the 5-HT reuptake inhibitor clomipramine haloperidolinduced catalepsy was found to be enhanced (Carter and Pycock 1977;Balsara et al 1979).…”