Mark Nickerson

Effect of Dibenamine on Renal Hypertension in Rats.

Summary 1. Oral administration of 100 mg/kg Dibenamine causes some reduction of blood pressure in both normotensive and renal hypertensive rats. The fall is usually greater and more prolonged in hypertensive animals. 2. The fall in blood pressure is due to the adrenergic blocking action of Dibenamine and does not follow the administration of larger doses of the adrenergically inactive N,N-dibenzyl-ethanolamine. 3. In 65% of the hypertensive animals tested, repeated daily doses of Dibenamine produced a persistent, but somewhat variable lowering of the blood pressure. The pressure usually returned to pretreatment levels in 3 to 4 days after the last administration of Dibenamine. 4. The bearing of these data on postulated neurogenic factors in experimental renal hypertension is discussed, and it is concluded that they do not support the contention that a greater neurogenic factor is involved in late than in early renal hypertension.

Effect of Dibenamine on Renal Function.

Summary 1. Six weekly intravenous injections of Dibenamine (20 mg/kg) failed to produce any detectable renal damage as measured by creatinine and PAH clearances in 5 trained, unanesthetized female dogs, even when the entire dose was injected within one minute so as to produce maximum toxic side-effects including prostration for 24 to 48 hours. 2. During maximal sympathetic blockade by Dibenamine, renal plasma flow was reduced, 10 to 34% (average 21%), probably on the basis of reduced systemic arterial pressure. However, the filtration fraction was sufficiently elevated to provide unaltered glomerular filtration. These alterations never persisted beyond the period of active adrenergic blockade. 3. We have been completely unable to substantiate the observations of Ogden7 on the renal toxicity of Dibenamine or to find any renal bask for his warning regarding its use. Even large doses of Dibenamine administered very rapidly appear to have no significant reno-toxic action.