The pharmacological effects of the various derivatives of choline are as follows. LD5Q, determined with 5 mice per dose group, in mgm./kgm. mouse: gamma-aminobutyryl- 3-5, butyryl- 115-0, propionyl -550-0, acetyl- 350-0. Gamma-aminobutyrylcholine is by far the most potent, its LD50 being about 1/100 of that of acetylcholine. Muscarinic and nicotinic actions of the choline esters (injected in the femoral vein) were determined by the fall of the carotid blood pressure before, and its rise after, atropinization (2-4 mgm.) in the cat anaesthetized with urethane. The muscarinic effect was most pronounced with acetylcholine; then followed propionyl-, butyryl- and gamma-amino-butyrylcholine, the potency decreasing exponentially in that order. Gamma-aminobutyrylcholine was peculiar in its action. It had no effect in doses smaller than 0-1 ml. of a 10~2 M solution, and this dose caused a slight but relatively prolonged fall (1 mm. mercury), then a rise, in blood pressure followed by death. For the nicotinic action of the choline esters, the order of efficacy was inverted, and the difference of potency between them was arithmetical. Gaonma-ammobutyrylcholine at a dose of 0-5 ml. of a 10~a M solution caused a distinct rise in blood pressure (15 mm. mercury), death following immediately.In assay with the eserinized frog rectus, an exponential gradient of potency similar to that of the muscarinic action on the blood pressure of the cat was noticed. Concentrations of the choline esters and the contractions which they bring about are: 10~s M gamma-aminobutyryl- 3 mm., 10~4 M. butyryl -14 mm., 10~5 M propionyl- 31 mm. and 10~6 M acetyl -12 mm. D-tubocurarine depressed the effect of all the choline esters. All the esters except gamma-aminobutyrylcholine caused an isolated piece of guinea pig ileum to contract. At concentrations of 5 x W~M: butyryl -14 mm., propinyl- 53 mm., and acetyl- 77 mm.; pretreatment with atropine blocked their action. However, gamma-anunobutyiylcholine had no action even at a concentration of 5 X 10~2 M. On the contrary, it elicited a slight anticholinergic action, and at 5 x 10~2 M depressed the contractile activity of 5-5 x 10~e M acetylcholine by 12-9 per cent (average of six experiments). The antihistaminic action of gamma-aminobutyrylcholine was more pronounced. Contraction of the ileum of the guinea pig by 5-4 X 10~8 M histamine was completely blocked at 5 x 10~s M9 and it was depressed 82 6 per cent at 5 X 10~e M. However, when the concentration of histamine was raised to 5-4 x 10~6 M, gamma-aminobutyrylcholine scarcely affected the contraction.Histamine and acetylcholine are stimulators of gastric secretion, which makes experiments on the effect of choline esters on gastric secretion interesting. The result of experiments performed on the rat by the method of Friedman and Sandweiss6 is shown in Table 1. Gamma-aminobutyrylcholine inhibited secretion, and even 0-05 ml. of 10~M solution (intraperitoneally) was apparently effective in reducing free hydrochloric acid as well as total acidity. The other choline esters acted like acetylcholine, enhancing acid secretion, though only at fairly high doses. Table i. EFFECT OF CHOLINE ESTERS ON THE GASTRIC SECRETION OF THE BAT (AVERAGE OF THREE EXPERIMENTS)Free hydro- Total No. ofEsters Dose Volume chloric acidity experi- (ml.) acid (N) ments(m.equiv.) Control 0-5 28-5 0-059 6Acetyl- choline 10~2 M, 1 -0 ml. 0-57 37-6 0-084 5Gamma- amino- 10-M, 0-05 ml. 0-4 0 0-037 3 butyryl-choline Butyryl- 10- M, 0-05 ml. 10~4M, 0-05 ml. 10"1 M, 0 -05 ml. 0-58 0-32 0-5 0 12-0 33-3 0-041 0-048 0-083 3 3 3choline 10~8 M, 0 -05 ml. 0-47 26-3 0-057 3 Pro-pionyl- 1M, 0-05 ml. 0-47 24-0 0-093 3 choline 10"1 M, 0 -05 ml. 0-43 21-7 0-08 3The observations described show that gamma-aminobutyrylcholine behaves peculiarly and suggest that it may be an inhibitory neurotransmitter. Glyeyl-choline, an ester like gamma-aminobutyrylcholine, but with the amino-group in the alpha- instead of the gamma-position, had an action similar to, but much weaker than, acetylcholine.