RELATIONSHIP BETWEEN PHARMACOLOGICAL ACTIONS ON THE MAMMALIAN ILEUM AND CHEMICAL STRUCTURE OF γ-AMINOBUTYRIC ACID
1961 Volume 11 Issue 3 Pages 229-237
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1961 Volume 11 Issue 3 Pages 229-237
The effects of GABA, its derivatives and their related compounds on the isolated ileum of the guinea-pig, rabbit and cat were investigated.
1. GABA had three types of effect on the guinea-pig ileum under various conditions; i.e. sustained tone-increasing, or relaxing or transient tone-increasing one followed by relaxation.
2. Other ω-amino-acids, such as glycine, δ-aminovaleric acid and ε-aminocaproic acid had no effect. Only β-alanine at 10-2 M/1 produced sometimes only a slight relaxation.α-amino-n-butyric acid and β-amino-isobutyric acid had no effect.
3. 4-Aminobutanol and N-methyl-4-aminobutanol at very high concentrations had a slight stimulant action, although n-butyric acid had no effect.
4. N-Substitution with acetyl, phenyl, butyl or methyl group reduced relaxing activity of GABA.
5. Methylesterification of GABA strengthened its stimulant activity. The stimulant effects of methylesters were antagonized by atropine.
6. As the chemical structure of GABA became more similar to that of Ach, its stimulant activity became progressively higher. However, even N-trimethyl-GABA-methylester, whose effect was strongest among the methylesters, was by far weaker than Ach.
7. N-Ethylation and N-butylation weakened the stimulant effect of GABAmethylester and N-phenylation reversed it into a relaxing one.
8. N-Methyl-GABA-ethylester had a weaker stimulant effect than N-methyl-GABA-methylester, and N-methyl-GABA-butylester and N-methyl-GABA-benzylester had a marked relaxing effect.
9. N-Methyl-GABA-ethylester had a weak relaxing action in lower concentrations, but a stimulant effect in higher concentrations. On the contrary, N-methylbutylester had a weak stimulant effect in lower concentration, but a strong relaxing one in higher concentrations.
10. The effect of GABOB was similar to that of GABA. But, the effects of GABOB and GABOB-methylester were weaker respectively than those of GABA and GABA-methylester. OH-group at β-position reduced the activity of GABA.
11. Nicotinic acid, isonicotinic acid and their methylesters produced a slight relaxation.
12. The rabbit ileum responded to above mentioned GABA-derivatives with similar manners, but with less sensitivity than the guinea-pig ileum.
13. The cat ileum reacted to these substances with almost the same manners and sensitivity as the guinea-pig ileum.
14. The relation between the structure and the effects of GABA was discussed.
