Sedative and anticonvulsant effects of adenosine analogs in mouse and rat.
Sedative and anticonvulsant effects of adenosine analogs in mouse and rat.
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发表时间：
1982
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通讯作者：
T. Dunwiddie;T. Worth
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作者：
T. Dunwiddie;T. Worth
研究了L-苯异丙基腺苷、环己基腺苷和2-氯腺苷对小鼠和大鼠行为和生理的影响。腺苷的这些类似物是激动剂，其在体外以高亲和力结合推定的中枢A1受体。相对低剂量的这些药物腹腔注射产生明显的镇静和体温降低;较高剂量导致自发运动活动几乎完全停止以及一些共济失调。这些类似物也拮抗由具有不同作用机制的各种惊厥药引起的癫痫发作。在类似物的抗惊厥效力中观察到的差异表明，这些作用不是由这些药物与单一类别的腺苷受体的相互作用产生的。特别是，2-氯腺苷和环己基腺苷似乎比L-苯基异丙基腺苷彼此更相关。由于L-苯基异丙基腺苷的某些抗惊厥作用不被腺苷拮抗剂茶碱逆转，也不被其他类似物所共有，因此这些作用可能反映了由其他非嘌呤能受体介导的作用。虽然苯二氮卓类药物也具有镇静、降低体温和抗惊厥的特性，但对苯二氮卓类药物的反应可与对腺苷激动剂的反应明显分离。
The behavioral and physiological effects of L-phenylisopropyladenosine, cyclohexyladenosine and 2-chloroadenosine were examined in mice and rats. These analogs of adenosine are agonists which bind with high affinity to putative central A1 receptors in vitro. Relatively low doses of these drugs administered i.p. produced marked sedation and hypothermia; higher doses resulted in an almost complete cessation of spontaneous motor activity as well as some ataxia. These analogs also antagonized seizures elicited by a variety of convulsants with different mechanisms of action. The differences observed in the anticonvulsant potencies of the analogs suggest that these effects are not produced by the interaction of these drugs with a single class of adenosine receptor. In particular, 2-chloroadenosine and cyclohexyladenosine appear to be more related to each other pharmacologically than to L-phenylisopropyladenosine. Because some of the anticonvulsant actions of L-phenylisopropyladenosine are not reversed by the adenosine antagonist theophylline, and are not shared by the other analogs, these may reflect actions mediated by other, perhaps nonpurinergic receptors. Although benzodiazepines also have sedative, hypothermic and anticonvulsant properties, responses to benzodiazepines can be clearly dissociated from responses to the adenosine agonists.