The Effect of Reserpine on the Pressor Response to Injection of 2‐halogenoethylamine

Abstract

Dibenamine-like compounds sometimes caused an increase in blood pressure when injected intravenously in mammals. This response varied with species, with the preparation, and with the structure of the compound. The response became smaller after repeated injections. In spinal atropinized rats injected with hexamethonium 5 mg/kg this pressor effect produced by injection of the adrenaline antagonist, compound AT3 [ethylfluoren-9-yl(2-iodoethyl)amine hydriodide], was reduced by prior treatment for five days with 1 mg/kg reserpine. Acute adrenalectomy also reduced this effect of the adrenaline antagonist; reserpine plus adrenalectomy abolished it. Subsequent injection of adrenaline and noradrenaline restored it.It is well known that compounds like phenoxybenzamine [benzyl-(2-chlorethylXlmethyl-2-phenoxyethyl)amine] antagonize the pressor response to injected catechol amines and lower the blood pressure for prolonged periods. Less attention has been paid to the acute pressor response which may be caused by intravenous injection of the 2-halogenoethylamine itself. A study of this phenomenon may reveal an aspect of the activity of these compounds which is an essential preliminary to their antagonistic effect. METHODSDemonstration of the pressor action. Carotid blood pressure was recorded manometrically from the following preparations: (a) dogs anaesthetized with 40 mg/kg pentobarbitone sodium intravenously and injected with 5 mg of atropine sulphate subcutaneously, <b) atropinized spinal cats, (c) atropinized spinal rats with or without injection of 5 mg/kg ,of hexamethonium hydrobromide and with and without acute bilateral adrenalectomy. Three 2-halogenoethylamines were tested, (2-bromoethyl)ethyl(naphth-1-ylmethyl)amine hydrobromide (SY28 or Ji1, Graham & Lewis, 1953), (p-chlorobenzyl)(2-chloroethyl)ethylamine hydrochloride (JFA8) and ethylfluoren-9-yl(2-iodoethyl)amine hydriodide (AT3, Graham, 1960). In all cases the compounds were dissolved from the crystalline state in minimal volumes of acetone, diluted with neutral saline, and injected intravenously at once in a fixed volume in a dosage of 10 pg/kg of compound AT3 to 1.0 mg/kg of compound Jl1. For rats this was 0.1 ml. per injection, washed in with 0.2 ml. of saline. Control observations were always made with the same volume of solvent similarly injected. The injections were repeated three times at intervals of 15 min with or without the interspersion of injections of 4 ilg/kg adrenaline or noradrenaline (calculated as base) in cats and dogs, 1 ug/kg in rats.Isolated preparations. Doses of 1 pg to 1 mg of each of the three compounds were injected into the fluid perfusing standard preparations of (a) isolated rabbit hearts (each drug was tested on three preparations) and isolated perfused hearts of young cats and (b) perfused vessels of the rabbit ear.Effect of reserpine on the pressor action. Twenty-five male hooded rats of approximately 300 g were treated with 1 mg atropine, a spinal preparation was made and hexamethonium