THE BIOCHEMORPHOLOGY OF NICOTINE

I. OBSERVATIONS ON THE EFFECT OF PROGRESSIVE DEGRADATION OF THE PYRROLIDINE RING

¹ From the Department of Pharmacology Medical College of Virginia, Richmond

The effect of progressive degradation of the pyrrolidine ring of the nicotine molecule on acute toxicity (mouse) and blood pressure (dog) has been studied. Acute toxicity was decreased by:

(a) N-demethylation.

(b) Opening of the pyrrolidine ring between the N-C linkage, the decrease being greatest when the cleavage occurred between the nitrogen and the 5 position.

(c) Shortening of the resultant side chain following N-C cleavage between the 1 and 5 positions.

Furthermore, in all instances reported, deamination altered the characteristic response from a convulsant one to an anesthetic one.

Pressor potency was decreased by:

(a) N-demethylation provided the nitrogen was linked to the first carbon of a beta substituted pyridyl molecule; in all other pairs studied demethylation increased pressor potency.

(b) Opening of the pyrrolidine ring between the N-C linkage, the decrease being greatest when the cleavage occurred between the 1 and 5 positions. In the latter case, shortening of the resultant side chain increased pressor potency.

(c) Deamination. All deaminated derivatives studied were depressor and those compounds that were originally depressor despite the presence of an amino group became more so on deamination.