Abstract

Studies on the pharmacology of N,N, dibenzyl-β-chloroethylamine (Dibenamine) revealed the following:

1. The primary toxic effects of Dibenamine are local tissue damage and central excitation. When central excitation is prevented by slow administration or sedation, large intravenous doses are well tolerated.

2. Dibenamine produces its systemic effects when administered orally, subcutaneously, intramuscularly, intraperitoneally or intravenously.

3. Dibenamine blocks and reverses the vasopressor response to all doses of epinephrine investigated (0.1 µgm. to 10 mgm./kgm). This adrenergic blocking action may persist for three to four days after a single injection of Dibenamine.

4. Dibenamine does not prevent an increase in heart rate and cardiac output in response to epinephrine.

5. Dibenamine blocks the excitatory responses of smooth muscle to sympathetic nerve stimulation and to epinephrine, as shown by:

(a) Reversal of the vasopressor response to eléctrical stimulation of the splanchnic nerves, both in intact animals and after bilateral adrenalectomy.

(b) Reversal of the vasopressor response to short periods of anoxia.

(c) Prevention of the splenic contraction largely responsible for the increase in circulating erythrocytes and mononuclear leukocytes normally induced in unanesthetized cats by a short struggle.

(d) Prevention or marked reduction of mydriasis and retraction of the nictitating membrane in response to electrical stimulation of the cervical sympathetic nerves or in response to injected epinephrine (even after denervation).

(e) Prevention of the pilomotor response to electrical stimulation of the lower abdominal sympathetic chains.

(f) Reversal of the nicotinic vasopressor response to large doses of choline esters in atropinized animals.

(g) Reversal of the epinephrine-induced contraction of the non-pregnant rabbit uterus both in vivo and in vitro.

6. Dibenamine provides protection against the lethal effects of several times the L.D.₁₀₀ of epinephrine.

7. The cardiac irregularities elicited by epinephrine in dogs anesthetized with cyclopropane are almost completely prevented by Dibenamine.

8. Preliminary experiments indicate that Dibenamine may be effective in lowering the blood pressure of rats with experimental renal hypertension.

9. Dibenamine does not prevent the inhibitory effects of epinephrine, such as relaxation of the intestine or the non-pregnant cat uterus. The rise in blood glucose and the hyperpnea induced by epinephrine are likewise unaffected.

10. The reversal of adrenergic vasopressor effects by Dibenamine is not altered by atropine, Benadryl or Pyribenzamine, or by the anesthetic employed.

11. Dibenamine apparently does not promote the in vitro or in vivo destruction of epinephrine.

These results are viewed as indicating that Dibenamine probably acts directly upon effector cells to prevent excitatory responses to epinephrine or sympathin E. The possible clinical usefulness of the adrenergic blocking action of Dibenamine is discussed.