Polc P, Laurent J P, Scherschlicht R, Haefely W
Naunyn Schmiedebergs Arch Pharmacol. 1981 Jul;316(4):317-25. doi: 10.1007/BF00501364.
This is an electrophysiological study in cats and rats of the imidazobenzodiazepinone derivative, Ro 15-1788, the first representative of specific benzodiazepine antagonists. (1) In unanaesthetized spinal cats, 1-10 mg kg-1 Ro 15-1788 i.v. did not affect segmental dorsal root potentials (DRPs), polysynaptic ventral root reflexes (VRRs), Renshaw cell responses to antidromic ventral root volleys and spontaneous gamma-motoneurone activity. However, at 1 mg kg-1 i.v., it antagonized the enhancement of DRPs as well as the depression of polysynaptic VRRs, Renshaw cell discharges and gamma-motoneurone activity induced by meclonazepam (0.1 mg kg-1 i.v.), diazepam (0.3 mg kg-1 i.v.) or zopiclone (1 mg kg-1 i.v.). The same dose of Ro 15-1788 failed to reduce similar effects of phenobarbital (10 mg kg-1 i.v.) on spinal cord activities. (2)In unanaesthetized "encéphale isole" rats, 3 mg kg-1 Ro 15-1788 i.v. abolished the decrease induced by 5 mg kg-1 midazolam i.v. of spontaneous multiunit activity (MUA) in the substantia nigra pars compacta, nucleus raphé dorsalis, nucleus locus coeruleus and the CAl area of the hippocampus dorsalis, but not the decrease produced by 10mg kg-1 pentobarbital i.v. Ro 15-1788 (12mg kg-1 i.v.) by itself did not affect MUA in the substantia nigra, but slightly depressed MUA in the other 3 areas. (3) In intact immobilized rats, the increase of power induced by 1 mg kg-1 flunitrazepam i.v. in the 0.5-48 Hz range of the electrocorticogram as well as in the 0.5-8 Hz, 8-32 Hz and 32-48 Hz frequency bands was transiently abolished by 5 mg kg-1 Ro 15-1788 i.v. (4) In unrestrained cats, 5 mg kg-1 Ro 15-1788 i.p. had no effect on the electrical threshold for eliciting a rage reaction evoked by electric hypothalamic stimulation, but abolished the threshold increase caused by 1 mg kg-1 diazepam i.p. These results are in line with biochemical and behavioural findings and support the selective antagonism by Ro 15-1788 of central effects of benzodiazepines through an interaction at benzodiazepine receptors.
这是一项针对咪唑并苯二氮䓬酮衍生物Ro 15 - 1788（特异性苯二氮䓬拮抗剂的首个代表药物）在猫和大鼠身上进行的电生理研究。（1）在未麻醉的脊髓猫中，静脉注射1 - 10 mg/kg的Ro 15 - 1788对节段性背根电位（DRP）、多突触腹根反射（VRR）、Renshaw细胞对逆向腹根冲动的反应以及自发的γ运动神经元活动均无影响。然而，静脉注射1 mg/kg时，它能拮抗氯硝西泮（静脉注射0.1 mg/kg）、地西泮（静脉注射0.3 mg/kg）或佐匹克隆（静脉注射1 mg/kg）所诱导的DRP增强以及多突触VRR、Renshaw细胞放电和γ运动神经元活动的抑制。相同剂量的Ro 15 - 1788未能减轻苯巴比妥（静脉注射10 mg/kg）对脊髓活动的类似影响。（2）在未麻醉的“孤立脑”大鼠中，静脉注射3 mg/kg的Ro 15 - 1788可消除静脉注射5 mg/kg咪达唑仑所诱导的黑质致密部、背侧中缝核、蓝斑核以及背侧海马CA1区自发多单位活动（MUA）的减少，但不能消除静脉注射10 mg/kg戊巴比妥所产生的减少。静脉注射12 mg/kg的Ro 15 - 1788本身对黑质中的MUA无影响，但会轻微抑制其他3个区域的MUA。（3）在完整的固定大鼠中，静脉注射5 mg/kg的Ro 15 - 1788可暂时消除静脉注射1 mg/kg氟硝西泮在脑电图0.5 - 48 Hz范围内以及0.5 - 8 Hz、8 - 32 Hz和32 - 48 Hz频段所诱导的功率增加。（4）在未束缚的猫中，腹腔注射5 mg/kg的Ro 15 - 1788对下丘脑电刺激诱发愤怒反应的电阈值无影响，但可消除腹腔注射1 mg/kg地西泮所导致的阈值升高。这些结果与生化和行为学研究结果一致，并支持Ro 15 - 1788通过与苯二氮䓬受体相互作用对苯二氮䓬类药物的中枢效应具有选择性拮抗作用。
