Selectivity of serotonergic drugs for multiple brain serotonin receptors. Role of [3H]-4-bromo-2,5-dimethoxyphenylisopropylamine ([3H]DOB), a 5-HT2 agonist radioligand.
Selectivity of serotonergic drugs for multiple brain serotonin receptors. Role of [3H]-4-bromo-2,5-dimethoxyphenylisopropylamine ([3H]DOB), a 5-HT2 agonist radioligand.
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血清素药物对多种脑血清素受体的选择性。
DOI：
10.1016/0006-2952(87)90643-5
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发表时间：
1987
影响因子：
5.8
通讯作者：
Glennon,RA
中科院分区：
文献类型：
--
作者：
Titeler,M;Lyon,RA;Davis,KH;Glennon,RA
用放射配体结合试验测定了5-HT 1A、5-HT 1B、5-HT 1C和5-HT 2受体的5-羟色胺受体激动剂和拮抗剂的亲和力。用激动剂放射性配体[3 H]-8-羟基-2-（二正丙基氨基）-四氢萘[3 H]-8-OH-DPAT、[3 H]-5-HT和[3 H]美舒麦角碱标记5-HT 1位点。用拮抗剂[3 H]酮色林或激动剂[3 H]-4-溴-2，5-二甲氧基苯基异丙胺（[3 H] DOB）标记5-HT 2受体。当使用拮抗剂放射性配体[3 H]酮色林测定5-HT 2受体亲和力时，发现激动剂化合物的表观5-HT 1受体选择性比使用激动剂放射性配体[3 H] DOB时高50- 100倍。当[3 H]酮色林用作5-HT 2放射性配体时，Quipazine对5-HT 2的作用仅为5-HT 1A受体的3倍。当[3 H] DOB被用作5-HT 2放射性配体时，喹帕嗪被确定为对5-HT 2受体的效力比对5-HT 1A受体的效力高100倍。1-（3-三氟甲基苯基）哌嗪（TFMPP）是一种特异性5-HT 1B受体激动剂，当[3 H]酮色林作为5-HT 2放射性配体时，TFMPP对5-HT 1B受体的作用比5-HT 2受体强10倍。以[3 H] DOB为5-HT 2放射性配体时，TFMPP对5-HT 1B和5-HT 2受体的作用是等效的。用5-HT 2受体拮抗剂[3 H]酮色林，对一系列5-羟色胺受体激动剂也观察到类似的低估5-HT 2受体选择性和/或高估5-HT 1A或5-HT 1B受体选择性的模式。拮抗剂受体的选择性不受显着的5-HT 2受体测定的性质。这些数据表明，用拮抗剂标记5-HT 2受体和激动剂标记5-HT 1受体，可能高估了5-HT 1受体的选择性。这可能是5-羟色胺药物开发中一个特别严重的问题，因为据报道，与5-HT 2受体有效相互作用的药物具有精神活性和/或致幻性。
The affinities of putative serotonin receptor agonists and antagonists for 5-HT 1A, 5-HT 1B, 5-HT 1C, and 5-HT 2 receptors were assayed using radioligand binding assays. The 5-HT 1 sites were labeled with the agonist radioligands [3 H]-8-hydroxy-2-(di-n-propylamino)-tetralin [3 H]-8-OH-DPAT,[3 H]-5-HT, and [3 H] mesulergine. The 5-HT 2 receptor was labeled with the antagonist radioligand [3 H] ketanserin or the agonist radioligand [3 H]-4-bromo-2, 5-dimethoxyphenylisopropylamine ([3 H] DOB). The apparent 5-HT 1 receptor selectivity of agonist compounds was found to be 50-to 100-fold higher when the 5-HT 2 receptor affinity was determined using the antagonist radioligand [3 H] ketanserin than when the agonist radioligand [3 H] DOB was used. Quipazine, a putative specific 5-HT 2 agonist, appeared to be only 3-fold more potent at 5-HT 2 than at 5-HT 1A receptors when [3 H] ketanserin was used as the 5-HT 2 radioligand. When [3 H] DOB was used as the 5-HT 2 radioligand, quipazine was determined to be 100-fold more potent at 5-HT 2 receptors than at 5-HT 1A receptors. 1-(3-trifluoromethylphenyl) piperazine (TFMPP), a putative specific 5-HT 1B receptor agonist was apparently 10-fold more potent at 5-HT 1B receptors than at 5-HT 2 receptors when [3 H] ketanserin was used as the 5-HT 2 radioligand. When [3 H] DOB was used as the 5-HT 2 radioligand, TFMPP was found to be equipotent at 5-HT 1B and 5-HT 2 receptors. Using the 5-HT 2 antagonist radioligand [3 H] ketanserin, a similar pattern of underestimating 5-HT 2 receptor selectivity and/or overestimating 5-HT 1A or 5-HT 1B receptor selectivity was observed for a series of serotonin receptor agonists. Antagonist receptor selectivity was not affected significantly by the nature of the 5-HT 2 receptor assay used. These data indicate that, by using an antagonist radioligand to label 5-HT 2 receptors and agonist radioligands to label 5-HT 1 receptors, the 5-HT 1 receptor selectivity may be overestimated. This may be an especially severe problem in serotonin drug development as drugs that interact potently with 5-HT 2 receptors have been reported to be psychoactive and/or hallucinogenic.
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伊沙匹隆抑制中缝背核和海马结构的神经元活动。
影响因子：
5
作者：
A. Basse;G. Rebec
通讯作者：
G. Rebec
丁螺环酮的神经药理学。
影响因子：
3.6
作者：
L. Riblet;A. S. Eison;M. Eison;Duncan P. Taylor;D. Temple;C. P. Vandermaelen
通讯作者：
C. P. Vandermaelen
影响因子：
4.7
作者：
BATTAGLIA, G;SHANNON, M;TITELER, M
通讯作者：
TITELER, M
血清素受体激动剂和拮抗剂对松鼠猴日程控制行为的影响。
DOI：
--
发表时间：
1985
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Brady,LS;Barrett,JE
通讯作者：
Barrett,JE
影响因子：
5
作者：
HJORTH, S;CARLSSON, A
通讯作者：
CARLSSON, A