Peterson S L
Department of Medical Pharmacology and Toxicology, Texas A & M University, College Station 77843.
Eur J Pharmacol. 1991 Jul 9;199(3):341-8. doi: 10.1016/0014-2999(91)90498-f.
This study evaluated a possible mechanism by which glycine potentiates the activity of anticonvulsant drugs against maximal electroshock seizures in rats. Administered concurrently, glycine (40 mmol/kg p.o.) significantly enhanced the anticonvulsant effect of phenobarbital, carbamazepine and phenytoin as determined by the occurrence of tonic hindlimb extension. Likewise, concurrent administration of the strychnine-insensitive glycine receptor agonist, D-serine (20 mmol/kg p.o.) significantly enhanced the anticonvulsant effect of phenobarbital, carbamazepine and phenytoin. L-Serine was ineffective. Administration of the strychnine-insensitive glycine receptor antagonist, 7-chlorokynurenic acid (100 nmol i.c.v.), significantly antagonized the potentiation of anticonvulsant activity induced by glycine co-administered with either phenobarbital or phenytoin. 7-Chlorokynurenic acid did not block tonic hindlimb extension when administered alone and did not affect the activity of the anticonvulsants in the absence of glycine. These results provide evidence for the potentiation of certain anticonvulsant drugs by glycine as a specific effect that may be mediated by the strychnine-insensitive glycine receptor.
本研究评估了甘氨酸增强抗惊厥药物对大鼠最大电休克惊厥作用的一种可能机制。同时给予甘氨酸（40 mmol/kg口服）时，通过强直性后肢伸展的发生情况测定，其显著增强了苯巴比妥、卡马西平和苯妥英的抗惊厥作用。同样，同时给予对士的宁不敏感的甘氨酸受体激动剂D-丝氨酸（20 mmol/kg口服）也显著增强了苯巴比妥、卡马西平和苯妥英的抗惊厥作用。L-丝氨酸则无效。给予对士的宁不敏感的甘氨酸受体拮抗剂7-氯犬尿氨酸（100 nmol脑室内注射），可显著拮抗与苯巴比妥或苯妥英共同给药时甘氨酸诱导的抗惊厥活性增强作用。单独给予7-氯犬尿氨酸时并不阻断强直性后肢伸展，且在无甘氨酸存在时不影响抗惊厥药物的活性。这些结果为甘氨酸增强某些抗惊厥药物的作用提供了证据，这一特定效应可能由对士的宁不敏感的甘氨酸受体介导。
