Effects of p-chlorophenylalanine, α-methyl-p-tyrosine, morphine and chlorpromazine on prostaglandin E1 hyperthermia in the rabbit

Prostaglandin E₁ (PGE₁) has been proposed as the mediator of pyrogen fever. Pyrogen fever has been shown to be enhanced in rabbits pretreated with p-chlorophenylalanine (p-CPA) but depressed in animals pretreated with α-methyl-p-tyrosine (α-MPT). In the present study α-MPT paradoxically enhanced the onset of hyperthermia produced by PGE₁ (5.0 μg) injected into a lateral ventricle. However PGE₁ hyperthermia was not affected by pretreatment with p-CPA, chlorimipramine HCl (5 mg/kg i.v.) or methysergide bimaleate (1 mg/kg i.v.). PGE₁ (0.5 μg) hyperthermia was not altered by either α-MPT or p-CPA pretreatment. These results suggest that if PGE₁ is the mediator of pyrogen fever in the rabbit, the biogenic amines exert their effects prior to the release of PGE₁. Morphine sulphate (10 mg/kg i.v.) and chlorpromazine HCl (5 mg base/kg i.v.) blocked PGE₁ hyperthermia whereas benztropine mesylate (0.2 mg/kg i.v.) was ineffective as an antagonist.