Biochemical and pharmacological effects of fluperlapine on noradrenaline and acetylcholine systems in some rodent, bovine and crustacean preparations.
Fluperlapine was compared with clozapine, chlorpromazine, haloperidol and imipramine regarding its effects on some cholinergic and noradrenergic animal systems. Fluperlapine and clozapine showed the most pronounced anticholinergic effects. Fluperlapine was equipotent with clozapine in displacing [3H]-QNB from muscarinic receptors of the calf cerebral cortex (IC50 about 15 nM). In the mydriasis test in the mouse and in the crayfish hindgut bioassay the differences between fluperlapine and clozapine were small. Like the other antischizophrenic drugs tested, fluperlapine displayed a marked affinity for alpha 1-adrenoceptors (calf cerebral cortex: IC50 about 10 nM) but a negligible affinity for alpha 2-adrenoceptors in the same tissue. Only clozapine showed a weak affinity for the latter receptor type. Fluperlapine was as effective as imipramine in antagonizing tetrabenazine-induced ptosis in the rat, the anti-ptotic effect remaining constant after up to ten daily drug administrations. Still, imipramine was stronger than fluperlapine as an inhibitor of the accumulation of [3H]-noradrenaline ([3H]-NA) in rat cerebral cortex slices. Fluperlapine's effects on the spontaneous and the electrically-induced release of [3H]-NA from rat cerebral cortex slices, with and without protriptyline, showed it to be an inhibitor of the reuptake of NA. The results indicate that the pharmacological profile of fluperlapine is similar to that of clozapine, with additional antidepressant properties.
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003400:Astacoidea; D002417:Cattle; D002540:Cerebral Cortex / Q000378:metabolism; D003984:Dibenzazepines / Q000494:pharmacology*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism*; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D011619:Psychotropic Drugs / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism
D014150:Antipsychotic Agents; D003984:Dibenzazepines; D011619:Psychotropic Drugs; D011942:Receptors, Adrenergic, alpha; D011976:Receptors, Muscarinic; C041528:fluperlapine; D000109:Acetylcholine; D009638:Norepinephrine