Abstract

Benzomethamine has high anticholinergic activity, similar to that of atropine and Banthine, as shown by assays on acetylcholine-induced spasms of the rabbit ileum, and methacholine-induced chromodacryorrhea in rats. Its activity in dogs closely parallels that of atropine and Banthine in blocking acetylcholine-and vagal-induced hypotension, and also gastric contractions due to stimulation of the vagus.

Benzomethamine is less effective than Banthine in blocking the contractile response of the urinary bladder to pelvic nerve stimulation.

The inhibitory activity of benzomethamine against pilocarpine-induced salivation in rabbits is only two-tenths that of atropine.

Benzomethamine can produce ganglionic blockade in higher doses; in this respect it is only two-tenths as active as TEA and thus less active than Banthine. Its neuromuscular blocking potency appears to be very low.

The acute toxicity of benzomethamine in mice and dogs, and the subacute three-week toxicity in rats is low. No evidence of central nervous system toxicity was noted. In contrast, the tertiary amine analogue in the dog demonstrated pronounced central nervous system toxicity with anticholinergic doses.

Benzomethamine is active on oral administration in dogs although the orally effective dose is considerably larger than the intravenously effective dose. The pharmacological activity is discussed in relation to the absorption and physiological disposition. It is concluded that although benzomethamine is relatively stable metabolically, the factors of limited absorption, and rapid excretion emphasize the necessity of high intrinsic activity as a most important aspect of orally active anticholinergic quaternary ammonium agents.