STUDIES ON THE SYNERGISM AND ANTAGONISM OF DRUGS I. THE NON-PARASYMPATHETIC ANTAGONISM BETWEEN ATROPINE AND THE MIOTIC ALKALOIDS

¹ From the Department of Pharmacology and Materia Medica, Georgetown University, School of Medicine, Washington, D. C.

1. Vestibular nystagmus in unanesthetized or anesthetized animals may be elicited by pilocarpine or physostigmine and this action is opposed by atropine.

2. Stimulation of the ocular sympathetic system (dilatation of the pupil, slight exophthalmos, widening of the palpebral fissure, and withdrawal of the nictitating membrane), follows the injection of physostigmine, pilocarpine, acetyl-choline and nicotine. These sympathetic effects are reversed and inhibited by atropine. Atropine does not inhibit the ocular actions of epinephrine or of faradization of the cervical sympathetic. Thus atropine opposes pilocarpine and allied actions without depressing the structures acted upon by the pilocarpine and related alkaloids.

3. The sympathetic stimulant action upon the eye by pilocarpine and allied alkaloids is inhibited by ergotamine, and not by double superior cervical gangliectomy or double adrenalectomy. Thus, they directly stimulate sympathetic nerve ends.

4. Atropine opposes the stimulant effect of locally administered pilocarpine to the superior cervical ganglia.

5. Nicotine first stimulates and later depresses the sympathetic endings in the smooth muscles of the eye.

6. There is an antagonism between nicotine and atropine on the respiratory mechanism.

7. The problem of the antagonism is discussed.