Emetic, central nervous system, and pulmonary activities of rolipram in the dog

European Journal of Pharmacology
R J Heaslip, D Y Evans

Abstract

Rolipram was characterized for its emetic, behavioral, cardiovascular and pulmonary activities in dogs, to assess its systemic pharmacology and potential bronchodilatory selectivity. At doses > or = 0.1 mg/kg i.v., rolipram induced emesis, anxiety, and stepping behaviors in conscious dogs, and increased heart rate and cardiac contractility in anesthetized instrumented dogs not treated with a beta-adrenoceptor antagonist. Cardiovascular effects in anesthetized dogs were apparently related to rolipram's central nervous system activities, in that they were associated with a reversal pentobarbital-induced anesthesia and could be ablated by pentobarbital supplementation. Rolipram's reversal of anesthesia was confirmed in uninstrumented dogs, where rolipram shortened pentobarbital sleep time while increasing heart and respiratory rates. After intragastric administration, rolipram exhibited greater emetic potency (100% emesis at 0.1 mg/kg p.o.) and lesser bronchodilatory potency (ED50 = 0.04 mg/kg i.d.) than after i.v. administration. The data demonstrate that rolipram is a potent bronchodilator that produces central nervous system effects only at higher doses when administered i.v. to the dog. Administered intragastrically, however, ...Continue Reading

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