Perrault G, Morel E, Sanger D J, Zivkovic B
Laboratoires d'Etudes et de Recherches Synthélabo (L.E.R.S.), Bagneux, France.
Eur J Pharmacol. 1988 Nov 1;156(2):189-96. doi: 10.1016/0014-2999(88)90321-4.
The interaction of beta-CMC, an amino beta-carboline recently described as a selective antagonist of the sedative effect of diazepam, with zolpidem, an imidazopyridine hypnotic, which like beta-CMC binds preferentially to the omega 1 (BZ-1) site of the GABA benzodiazepine chloride channel receptor complex, was investigated. In mice, beta-CMC antagonized the effect of zolpidem against isoniazid-induced convulsions without affecting its activity against convulsions induced by pentylenetetrazole or electroshock. beta-CMC also antagonized the decrease in locomotor activity and the impairment in muscle strength provoked by zolpidem. In rats trained to discriminate zolpidem, beta-CMC antagonized both the interoceptive stimulus and the decrease in the rate of lever pressing produced by zolpidem. This selective antagonism, inhibition of effects of zolpidem exerted by low doses (locomotor activity and isoniazid-induced convulsions) as well as effects produced by high doses (muscle strength) but not those provoked by intermediate doses (pentylenetetrazole and electroshock-induced convulsions), could not be explained by a receptor occupancy hypothesis. These results suggest that the anticonvulsant and sedative effects of zolpidem do not involve the same receptor subtype and that the hypnoselective properties of zolpidem may be linked to its selectivity for the omega 1 (BZ-1) site of the GABAA receptor.
β-CMC是一种最近被描述为地西泮镇静作用选择性拮抗剂的氨基β-咔啉，它与唑吡坦（一种咪唑并吡啶催眠药，与β-CMC一样优先结合于GABA苯二氮䓬氯通道受体复合物的ω1（BZ-1）位点）之间的相互作用进行了研究。在小鼠中，β-CMC拮抗了唑吡坦对异烟肼诱导惊厥的作用，而不影响其对戊四氮或电休克诱导惊厥的活性。β-CMC还拮抗了唑吡坦引起的运动活动减少和肌肉力量损害。在经过训练以区分唑吡坦的大鼠中，β-CMC拮抗了唑吡坦产生的内感受性刺激和杠杆按压速率的降低。这种选择性拮抗作用，即低剂量（运动活动和异烟肼诱导的惊厥）时对唑吡坦作用的抑制以及高剂量（肌肉力量）时产生的作用，但不包括中等剂量（戊四氮和电休克诱导的惊厥）引起的作用，不能用受体占据假说来解释。这些结果表明，唑吡坦的抗惊厥和镇静作用不涉及相同的受体亚型，并且唑吡坦的催眠选择性特性可能与其对GABAA受体ω1（BZ-1）位点的选择性有关。
