THE USE AND LIMITATIONS OF ATROPINE FOR PHARMACOLOGICAL STUDIES ON AUTONOMIC EFFECTORS

The well known fact that atropine susceptibility is not an infallible criterion of cholinergic transmission is discussed in some detail. Various examples of atropine-resistant nerve effects have been considered, and the following types of atropine-resistance can be distinguished: 1) Apparent resistance which is due to destruction of atropine in the animal. This occurs in a proportion of rabbits, in which atropinesterase is present in the blood and in some tissues. The effect of atropine is then very brief and may erroneously be thought to be absent. 2) Atropine-resistance in cholinergic neuro-effector systems, as for example in intestinal preparations from some species, and possibly in the bladder. In the intestine corroborative evidence provided by anticholinesterases and by botulinum toxin strongly suggests that the nerve endings concerned are cholinergic, and therefore supports the theory put forward by Dale and Gaddum that this type of atropine-resistance is due to proximity of the nerve endings to the effector cells. It is pointed out that the classification of intestinomotor drugs by means of atropine is influenced by these considerations. 3) The secondary formation of an atropine-resistant pharmacological agent, e.g., of bradykinin in the salivary glands. Acetylcholine or chorda stimulation lead to the extrusion of a proteolytic enzyme capable of forming bradykinin from serum proteins. 4) Atropine-resistance due to non-cholinergic transmission. Two examples of this are considered: (a) antidromic trigeminal pupillary constriction; and (b) antidromic vasodilatation in the rabbit's ear. Confirmatory evidence from other sources indicates the non-cholinergic nature of these effects. 5) Several nicotinic actions of acetylcholine are relatively resistant to atropine, but can nevertheless be blocked by the alkaloid in appropriate concentrations.