The pharmacological actions of guanidinoacetic acid, γ-guanidinobutyric acid and γ-guanidinobutyryl-methylester were investigated and compared with those of ω-aminoacids.
1. Guanidinoacetic acid had a considerable stimulant effect on the isolated guinea-pig ileum at 10
-4-10
-3M/
l, while γ-guanidinobutyric acid produced rarely a very slight stimulant effect. Methylesterification of γ-guanidinobutyric acid strengthened markedly the stimulant effect. Its effect was weaker than that of γ-aminobutyryl-methylester and stronger than those of guanidinoacetic acid or ε-aminocapronyl-methyle ster.
2. Their stimulant effects on the guinea-pig ileum were antagonized by 0.1μg/m
l. atropine sulfate, as was the case with those of ε-aminoacids and their methylester.
3. These guanidino-derivatives had the similar effects on the isolated rabbit ileum.
4. The anatognistic actions of guanidinoacetic acid against stimulants (ACh, 5-HT, nicotine) on the guinea-pig ileum were much weaker than those of GABA. Guanidinoacetic acid had practically an anti-5-HT only.γ-Guanidinobutyric acid and its methylester had not any antagonistic action to the stimulants.
5. Guanidinoacetic acid had a slight depressant effect on blood pressure of anesthetized rabbits, while γ-guanidinobutyric acid produced it hardly.γ-Guanidinobutyryl-methylester had a much stronger depressant effect than γ-guanidinobutyric acid. Its effect was weaker than γ-aminobutyryl-methylester and stronger than γ-aminocapronyl-methyiester. The effect of guanidinoacetic acid was farinferior to that of GABA.
6. In anesthetized cats, the depressant effects of these guanidino-derivatives were more pronounced than in rabbits. Guanidinoacetic acid had rather a stronger effect than GABA in the cat.
7. The similarity and difference in the pharmacological actions of guanidinoderivatives and simple ω-aminoacid-derivatives were discussed in some details.
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