Penfluridol blockade of apomorphine: dependence of duration on species and endpoint

Penfluridol, at relatively low doses, blocks apomorphine-elicited emesis in dogs and apomorphine-elicited floor pecking in pigeons for over a month. In mice tested for apomorphine-elicited hypothermia, and in rats tested for apomorphine-elicited chewing behavior, however, the anti-apomorphine activity of penfluridol does not persist for longer than 2-3 days even when high doses of penfluridol are given. In rabbits tested for apomorphine-induced hyperthermia and gnawing, on the other hand, penfluridol blocks apomorphine for about a week. Thus, of the 5 species tested, only in rabbits does the duration of penfluridol's anti-apomorphine action approximate the 1-week duration reported from human therapeutic trials. In mice given high-dose penfluridol apomorphine consistently elevates body temperatures, rather than exerts its usual hypothermic response. Conversely, in rabbits given penfluridol apomorphine tends slightly to decrease body temperatures, rather than exert its usual hyperthermic response.