Ikonomidou-Turski C, Schwarz M, Turski L, Sontag K H
Eur J Pharmacol. 1986 Aug 22;128(1-2):1-7. doi: 10.1016/0014-2999(86)90550-9.
The muscle relaxant effect of phenobarbitone was studied in genetically spastic rats which exhibit spontaneous tonic activity in the electromyogram (EMG) of the gastrocnemius muscle. Phenobarbitone, 10-30 mg/kg i.p., reduced the tonic activity in the EMG of the gastrocnemius muscle of such rats in a dose- and time-dependent manner. The GABA antagonists bicuculline, 2 mg/kg i.p., and picrotoxin, 2 and 3 mg/kg i.p., reduced the muscle relaxant effect of phenobarbitone, 20 and 30 mg/kg. The benzodiazepine receptor antagonists, Ro 15-1788, 5 mg/kg, and CGS 8216, 5 mg/kg (doses which do not affect tonic activity in the EMG), failed to alter the depressant effect of phenobarbitone 30 mg/kg, in the EMG. Beta-Carboline-3-carboxylic acid methylester (beta-CCM), 2 mg/kg i.p., while not affecting the tonic activity in the EMG, reversed the depressant effect of phenobarbitone, 30 mg/kg. Both Ro 15-1788, 5 mg/kg, and CGS 8216, 5 mg/kg, prevented the reversal of the depressant action of phenobarbitone, 30 mg/kg, produced by beta-CCM, 2 mg/kg. The results indicate that the muscle relaxant action of phenobarbitone in genetically spastic rats is mediated via GABA-related mechanisms and add further support to the hypothesis that both Ro 15-1788 and CGS 8216 are specific antagonists at benzodiazepine receptors, devoid of intrinsic activity at moderate doses. The results also suggest that reversal of the muscle relaxant action of phenobarbitone by beta-CCM is mediated via a GABA/benzodiazepine receptor/chloride ionophore complex.
在基因痉挛大鼠中研究了苯巴比妥的肌肉松弛作用，这类大鼠腓肠肌肌电图（EMG）显示出自发性强直活动。腹腔注射10 - 30mg/kg的苯巴比妥，能以剂量和时间依赖性方式降低此类大鼠腓肠肌EMG中的强直活动。腹腔注射2mg/kg的GABA拮抗剂荷包牡丹碱和2mg/kg及3mg/kg的印防己毒素，可降低20mg/kg和30mg/kg苯巴比妥的肌肉松弛作用。苯二氮䓬受体拮抗剂Ro 15 - 1788（5mg/kg）和CGS 8216（5mg/kg）（这两个剂量不影响EMG中的强直活动），未能改变30mg/kg苯巴比妥在EMG中的抑制作用。腹腔注射2mg/kg的β-咔啉-3-羧酸甲酯（β-CCM），虽不影响EMG中的强直活动，但可逆转30mg/kg苯巴比妥的抑制作用。5mg/kg的Ro 15 - 1788和5mg/kg的CGS 8216均能阻止2mg/kg的β-CCM对30mg/kg苯巴比妥抑制作用的逆转。结果表明，苯巴比妥在基因痉挛大鼠中的肌肉松弛作用是通过GABA相关机制介导的，进一步支持了Ro 15 - 1788和CGS 8216是苯二氮䓬受体特异性拮抗剂的假说，在中等剂量时无内在活性。结果还提示，β-CCM对苯巴比妥肌肉松弛作用的逆转是通过GABA/苯二氮䓬受体/氯离子载体复合物介导的。
