Effect of piflutixol on turnover of catecholamines in mouse brain and rat corpus striatum.
Dopamine metabolism in vivo was studied after treatment with piflutixol (6-fluoro-9-[3-(4-(2-hydroxyethyl)piperidino)propylidene]-2-trifluoromethyl-thioxanthene) a novel thioxanthene derivative with potent neuroleptic properties and sedative effects. In mice piflutixol increased both noradrenaline (NA) and dopamine (DA) turnover rate measured as increased disappearance of 14C-amines formed from 14C-L-tyrosine. The ratio between the minimal effective doses for 14C-NA and 14C-DA disappearance was 2, which is of the same order of magnitude as obtained with cis(Z)-chlorprothixene, pimozide and chlorpromazine. After 14C-L-tyrosine the accumulation of 14C-dopamine was initially increased after which it decreased from day 4--5. These changes resemble those obtained after other neuroleptics and parallel the initial receptor blockade and the subsequent receptor supersensitivity found in pharmacological experiments (MOLLER NIELSEN et al. 1977). Piflutixol induced a rapid increase in both DOPAC and HVA with a maximal effect after 2--6 hours. After 2--3 days the levels had returned to normal. The doses of piflutixol which at 24 hours doubled the levels of DOPAC and HVA were found to be 0.055 and 0.021 mg/kg subcutaneously, respectively. It is concluded that piflutixol is a powerful and long lasting DA receptor blocking agent, which changes the synthesis and release of DA in a way similar to basic neuroleptics.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism; D010648:Phenylacetates / Q000378:metabolism; D051381:Rats; D013892:Thioxanthenes / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism
D002395:Catecholamines; D010648:Phenylacetates; D013892:Thioxanthenes; D014443:Tyrosine; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid