RELATIONSHIP BETWEEN THE HYPOTENSIVE ACTIVITY AND CHEMICAL STRUCTURE OF γ-AMINOBUTYRIC ACID IN THE RABBIT
1962 Volume 12 Issue 1 Pages 97-105
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1962 Volume 12 Issue 1 Pages 97-105
The effects of GABA and its derivatives on blood pressure, respiration and heart rate of the rabbit were investigated.
1. 4-Aminobutanol, N-methyl-4-aminobutanol and n-butyric acid had not any effect on blood pressure and respiration.
2. N-Methylation (N-methyl-GABA, N-dimethyl-GABA, N-trimethyl-GABA), Nphenylation and N-acetylation reduced profoundly the effects of GABA on blood pressure and respiration.
3. Esters of GABA had more or less apparent hypotensive effects on blood pressure.
4. GABA-methylester elicited a depressor response which was of the same order in magnitude, but extremely shorter in duration in comparison with that induced by GABA.
5. The depressant potency of GABA-methylester was not increased by N-monomethylation, but increased by 2-3-fold with N-dimethylation and by about 60-fold with N-trimethylation. The hypotensive effect of N-trimethyl-GABAmethylester was about 1/2 of that of ACh.
6. Other methylesters were compared for their hypotensive effects and placed the following descending order; N-methyl-GABA-methylester>N-butyl-GABAmethylester>N-phenyl-GABA-methylester>N-ethyl-GABA-methylester.
7. On the other hand, esters of N-methyl-GABA were placed in the following descending order methyl-GABA-methylester, methyl-GABA-benzylester>methyl-GABA-ethylester>methyl-GABA-butylester.
8. The above described derivatives usually did not produce any change in respiration.
9. Except of N-trimethyl-GABA-methylester, other methylesters did not elicit so appreciable bradycardia.
10.β-Hydroxy-GABA and its methylester had respectively a weaker hypotensive action than GABA and GABA-methylester.
11. Nicotinic acid and isonicotinic acid elicited rarely a depressor responce. Their methylesters had a stronger action than the acids, but a far weaker one than GABA-methylester or N-methyl-GABA-methylester.
12. The hypontensive action of methylesters of GABA was greatly reduced by atropinization. N-Trimethyl-GABA-methylester had a considerably strong nicotine action.
13. Intrathecally applied GABA elicited a much stronger and longer lasting depressor response than intravenously administered GABA. On the other hand, methylesters and N-substituents of GABA produced hardly a depressor response, when applied intrathecally.
