A NEW ANOREXIC AGENT, WY-5244: CARDIOVASCULAR ACTIONS AND INFLUENCE ON SYMPATHOMIMETIC AMINES

¹ Pharmacological Evaluation Section, Wyeth Laboratories, Inc., Radnor, Pennsylvania

1-(p-chlorophenyl-1,2,3,4,5,6-hexahydro-2,5-benzodiazocine diHCl, has been previously shown to possess anorexic properties. In the present study the i.v. injection of Wy-5244 to anesthetized dogs caused a fall in blood pressure (at 5-20 mg/kg) followed by a small rise (at 5 and 10 mg/kg). The magnitude of the depressor but not the pressor phase was dose-related. Cardiac output had a tendency to increase. In open-chest dogs blood pressure and right ventricular contractile force were initially depressed and then slightly augmented. Cardiac output decreased in these dogs. Oral administration to unanesthetized dogs or i.v. infusion in anesthetized animals caused negligible or small changes in pressure. Spinal or vagal section or a variety of autonomic blocking agents failed to inhibit the initial depressor response to rapidly injected Wy-5244 but the small secondary stimulant effect may have involved adrenergic mechanisms. The cardiovascular actions of Wy-5244, therefore, are minimal when the compound is infused or given orally and do not resemble those of amphetamine-like anorexic agents. Wy-5244 exerted characteristic effects on the cardiovascular actions of other agents. The compound antagonized the pressor and positive inotropic actions of several indirectly-acting sympathomimetic amines while the pressor effects of norepinephrine, epinephrine, phenylephrine, dimethylphenylpiperazinium and central vagal stimulation were unaltered or increased.