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Maj J, Baran L, Michaluk J, Palider W, Rawlow A.
“The Central Antiserotonin Activity of Neuroleptics”.
Pol.J.Pharmacol.Pharm.. 1978;30(2-3):407-09.
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Abstract
The central antiserotonin activity of neuroleptics was investigated. The action of promazine, chlorpromazine, triflupromazine, levomepromazine, perazine, prochlorperazine, trifluoperazine, thioperazine, perfenazine, fluphenazine, mepezine, thioridazine, clozapine, chlorprothixene, tiotixene, clopenthixol, flupentixol, haloperidol, spiperone and pimozide on the serotonin system was investigated by using 2 tests: "behavioral" syndrome elicited by L-5-hydroxytryptophan(L-5-HTP) (rats and mice) and the flex or reflex of the hind limb of the spinal rat. Cataleptic activity of the neuroleptics in rats was determined as a criterion of dopamine (DA)-receptor blockade. In part of the experiments, suitable compounds were used for comparison. All neuroleptics studied antagonized 5-HTP-syndrome. Their ED50s in this test were from 1.8 to 7.2 times lower than the F:DsG causing catalepsy. For butyrophenones only, the ED50s were similar in both the tests. The most potent antiserotonin activity was exhibited amongst phenothiazines, by perphenazine and fluphenazine, amongst thioxanthenes, by clopenthixol and flupentixol and amongst butyrophenones, by spiperone. The anti 5-HTP activity was not related to a blockade of DA receptors because: (1) there was no parallelism between the anti-5-HTP activity and catalepogenic effects of the neuroleptics; (2) the anti-5 -HTP activity was exhibited by some neuroleptics which d not induce catalepsy (promazine, mepazine, clozapine); (3) cyproheptadine, mianserin and danitracen possessed the anti-5 HTP activity but did not cause catalepsy (and even antagonized neuroleptic catalepsy). Atropine did not exhibit such an antagonism, but it was noticed after phenoxybenzamine and phentolamine. The flexor reflex was depressed by most neuroleptics in high enough doses. A number of neuroleptics (.g. prochlorperazine, trifluoperazine, perphenazine, fluphenazine, flupenthixol, spiperone) in doses lower than noradrenolytic ones, exhibited properties of 5-HT receptor blocker - having no influence on the flexor reflex, antagonized the potentiating action of LSD and fenfluramine. The anti-5-HT effect of neuroleptics may be of importance in their therapeutic efficacy in schizophrenia.
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