ADENOSINE RECEPTORS AND BEHAVIORAL ACTIONS OF METHYLXANTHINES
ADENOSINE RECEPTORS AND BEHAVIORAL ACTIONS OF METHYLXANTHINES
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DOI：
10.1073/pnas.78.5.3260
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发表时间：
1981-01-01
期刊：
影响因子：
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通讯作者：
DALY, JW
中科院分区：
文献类型：
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作者：
SNYDER, SH;KATIMS, JJ;DALY, JW
10种甲基黄嘌呤在小鼠体内的中枢兴奋作用与N6-[3H]环己基腺苷标记的腺苷受体的亲和力相关。甲基黄嘌呤对腺苷受体的亲和力与在行为有效剂量下达到的中枢水平一致。影响苯二氮卓受体结合所需的高得多的甲基黄嘌呤浓度与行为效力无关。N6-（l -苯异丙基）腺苷（L-PIA）是一种代谢稳定的腺苷类似物，对腺苷受体具有高亲和力，是一种非常有效的行为抑制剂，剂量低至0.05 μ mol/kg即可降低小鼠的运动活性。D异构体对腺苷受体的亲和力要小得多，作为中枢抑制剂的活性也要小得多。茶碱刺激运动活动并逆转L-PIA的抑制作用。单独给药时，咖啡因或1,7-二甲基黄嘌呤引起双相效应，低剂量时运动抑制，高剂量时运动刺激。当使用L-PIA时，即使是低剂量的咖啡因也会产生明显的刺激。单独给予3-异丁基-1-甲基黄嘌呤只会引起行为抑郁。像茶碱和咖啡因一样，异丁基甲基黄嘌呤可以逆转L-PIA引起的抑郁，将其转化为明显的运动刺激。甲基黄嘌呤的行为刺激作用涉及中枢腺苷受体的阻断。
Central stimulant actions of 10 methylxanthines in mice correlate with affinities for adenosine receptors labeled with N6-[3H]cyclohexyladenosine. Affinities of methylxanthines for adenosine receptors are consonant with central levels attained at behaviorally effective doses. The much higher concentrations of methylxanthines required to influence benzodiazepine receptor binding do not correlate with behavioral potency. N6-(L-Phenylisopropyl)adenosine (L-PIA), a metabolically stable analog of adenosine with high affinity for adenosine receptors, is an extremely potent behavioral depressant, reducing locomotor activity of mice at doses as little as 0.05 .mu.mol/kg. The D isomer, which has much less affinity for adenosine receptors, is much less active as a central depressant. Theophylline stimulates locomotor activity and reverses depressant effects of L-PIA. Caffeine or 1,7-dimethylxanthine, when administered alone, elicits biphasic effects, with locomotor depression at lower doses and stimulation at higher doses. When administered with L-PIA, even low doses of caffeine produce marked stimulation. 3-Isobutyl-1-methylxanthine given alone elicits only behavioral depression. Like theophylline and caffeine, isobutylmethylxanthine reverses the L-PIA evoked depression, converting it into pronounced locomotor stimulation. The behavioral stimulant effects of methylxanthines involve a blockade of central adenosine receptors.