ANTI-STIMULANT ACTIONS OF γ-AMINOBUTYRIC ACID AND ITS DERIVATIVES ON THE GUINEA-PIG ILEUM

抄録

The anti-stimulant (Ach, 5-HT, nicotine, histamine) actions of GABA and its derivatives on the guinea-pig ileum were investigated.
1. The anti-Ach action of GABA was weak and variable. The stimulant effect of 5×10^-10-10^-9 mole/l Ach was reduced by 42% on the average of 11 experiments.
2. The anti-Ach action of N-methyl-GABA was about a tenth of that of GABA. N-Dimethyl-GABA produced hardly it an N-trimethyl-GABA had a synergestic action with Ach.
3. N-Acetyl-GABA had a slightly weaker anti-Ach action than N-methyl-GABA and N-phenyl-GABA had a far weaker one.
4. GABA-methylester and N-methyl-GABA-methyiester had not any anti-Ach action. N-methyl-GABA-butylester and N-methyl-GABA benzylester had a much stronger anti-Ach action than GABA. N-phenyl-GABA-methylester had a slightly stronger one.
5. In the anti-5-HT action of GABA, N-substitution by methyl-, phenyl-and acetyl-group decreased the activity more severely than in the anti-Ach action.
6. N-Methyl-GABA-butylester and N-methyl-GABA-benzylester were similar to GABA as the antagonist of 5-HT. N-Phenyl-GABA-methylester was somewhat inferior to GABA.
7. The anti-nicotine action of GABA was also decreased by N-substitution with methyl-, phenyl-and acetyl-group. But, the reduction of potency by these structural changes was far less than in the anti-Ach action.
8. N-Methyl-GABA-butylester and N-methyl-GABA-benzylester had a very stronger anti-nicotine action than GABA, while N-phenyl-GABA-methylester had a slightly higher potency.
9. In all the actions above mentioned, N-methyl-GABA-butylester was somewhat superior to N-methyl-GABA-benzylester.
10. In all the actions, the activity of GABOB was a half or a third of that of GABA.
11. Methylesters of nicotinic acid and isonicotinic acid had a stronger anti-Ach action or anti-5-HT action than the acids and their activity was about a tenth of that of GABA. Methyl nicotinate and methyl isonicotinate were superior to their acids in anti-nicotine action, too, and their activities was more powerful than GABA.
12. GABA had not any anti-histamine action, but N-methyl-GABA-butylester and N-methyl-GABA-benzylester had a considerably strong action.