The pharmacology of penfluridol (R 16341) a new potent and orally long-acting neuroleptic drug

Abstract

R 16341, 4-(4-chloro- a, a, a-trifluoro-m-tolyl)-1[4,4-bis(p-fluorophenyl)butyl]-4-piperidinol is a new member of the potent and long-acting series of diphenylbutyl piperidine neuroleptics of which pimozide is the prototype. In animals the pharmacological profile of R 16341 resembles that of typical neuroleptic compounds. R 16341 is very potent by the oral route and has a longer duration of action than any other neuroloptic we have tested. At 4 times the minimum ED 50-value of the anti-apomorphine test in dogs, R 16341 has a duration of action of about 7 days. The onset of action of R 16341 is gradual and smooth and its peak effect is generally reached 24 to 48 hr after administration. R 16341 is relatively atoxic with a safety margin of 1:1000 in rats and dogs. Qualitatively R 16341 is more closely related to haloperidol and pimozide than to chlorpromazine, the side-effect liability is expected to be lower than that of chlorpromazine, when hypotensive and autonomic side-effects are concerned and to be lower than that of haloperidol when undesirable neurological side-effects are concerned.