ACTION OF PYRIDINE AND SOME DERIVATIVES OF PYRIDINE-3-CARBOXYLIC ACID OX NEUROMUSCULAR TRANSMISSION

¹ Department of Pharmacology and Biochemistry, Catholic University of Chile, Santiago, Chile

A study has been made of the action of pyridine and some of its derivatives on the quadriceps and soleus muscles of cats anesthetized with nembutal. These substances are without effect on the activity of serum cholinesterase.

Pyridine (P). At lower frequencies of stimulation, this drug is without effect on the indirectly stimulated muscle. It has a brief depressant effect on directly stimulated muscle. As the frequency is increased, an enhancement of the contraction is usually obtained; occasionally it depresses. With higher frequencies, it produces a brief depression, followed by a more prolonged reinforcement. It antagonises curare, and reinforces slightly the effect of prostigmine. The response of the muscle to acetylcholine is enhanced. It does not modify the effect of acetylcholine and potassium injected during indirect stimulation.

Pyridine-3-carboxylic acid (niacin, N). This drug is without effect on muscular contraction at low frequencies. At higher frequencies, it increases the tension; this is followed by a depression. It is antagonistic to curare and prostigmine. It is without effect on directly stimulated muscle. The response to acetylcholine is enhanced. It does not modify the effect of acetylcholine and potassium injected during indirect stimulation.

Pyridine-3-carboxylic acid amide (niacinamide, NA). This drug does not have any effect on contraction produced by indirect stimulation at the frequencies tested. It is antagonistic to curare. It increases the response to acetylcholine.

Ethyl ester of pyridine-3-carboxylic acid (EE). This substance decreases the tension developed during indirect stimulation at the frequencies studied. It increases the effects of curare and prostigmine. It produces a slight fall in the tension of directly stimulated muscle. It enhances the response of the muscle to acetylcholine; it increases the effects of acetylcholine and potassium injected during indirect stimulation.

Monoethyl-amide of pyridine-3-carboxylic acid (MA). This drug decreases the tension only at high frequencies of stimulation. It reinforces the action of curare and prostigmine.

Diethylamide of pyridine-3-carboxylic acid (Nikethamide, DA). This drug decreases the tension at high frequencies of stimulation. The effects of potassium and acetylcholine injected during indirect stimulation are enhanced.

The action of these drugs is discussed in relation to their chemical structure and may he interpreted in the light of their effects upon the threshold to acetylcholine.