Schellekens Kh

Chemistry and pharmacology of compounds related to 4-(4-hydroxy-4-phenyl-piperidino)-butyrophenone

SummaryHaloperidol (R 1625) is 50 to 100 times more active than chlorpromazine as an inhibitor of exploratory motor behaviour in rats. Emotional defaecation in rats is inhibited by both drugs at similar dose levels.

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.

Oxatomide, a new orally active drug which inhibits both the release and the effects of allergic mediators.

Oxatomide is a new potent inhibitor of anaphylactic and allergic reactions. After oral administration, the compound both inhibits the release of endogenous histamine and prevents the effects of exogenous histamine, at comparable doses. The combination of these effects appears to be the basis of the effectiveness of oxatomide in allergic reactions and may lead to clinical applications different from classical antihistaminics and from cromoglycate.