HOMATROPINE METHYLBROMIDE: A PHARMACOLOGICAL REEVALUATION

¹ Maltbie Laboratories, Morristown, N. J.

1. A comparative quantitative evaluation of homatropine methylbromide and atropine was made by using a quantal response in the rat. A linear relationship was found to exist between the doses of the drugs and various pharmacological responses: spasmolytic in vitro, spasmolytic in vivo, mydriatic and antisialagogue. The regression lines were quite parallel for the two compounds; the average effective dose was estimated graphically.

2. Homatropine methylbromide shares with atropine peripheral anticholinergic properties: a. In the rat in vitro it is comparatively nine times less spasmolytic. b. In vivo following subcutaneous administration homatropine methylbromide is nine times less active. Mydriatic side-effects are five times smaller and antisialagogue activity is twenty-six times less with homatropine methylbromide than with atropine. c. In the rat, following oral administration, homatropine methylbromide is much less active than atropine; it appears to be 21 times less effective on intestinal transit, 23 times less antisialagogue and 130 times less mydriatic than atropine.

3. Homatropine methylbromide injected intravenously in the cat depresses the response to preganglionic sympathetic stimulation, blocks the carotid sinus reflex resulting from carotid occlusion, prevents the pressor effects of ganglionic stimulants, (1-dimethyl-4-phenylpiperazinium iodide, DMPP) and (2-benzyl-phenyl--dimethylaminoethyl ether methiodide, BPDEA), and blocks the nicotinic response to acetylcholine.

Homatropine methylbromide is about four times more potent than atropine in depressing transmission across the superior cervical ganglion; moreover, when other criteria of ganglionic activity are used, atropine is ineffective at the dosage level used.

Orally in the cat homatropine methylbromide does not show significant ganglionic blockade up to 200 mgm./kgm.

4. Homatropine methylbromide is from one and one-half to four times more toxic than atropine sulfate in the rat and mouse following intraperitoneal and subcutaneous routes of administration; it is, on the contrary, one and one-half to four times less toxic following oral administration.

5. The difficulties in testing for parasympathetic ganglionic blockade in the case of any peripheral anticholinergic agent make it impossible to conclude whether homatropine methylbromide blocks the parasympathetic ganglia.