Kalkman H O, Harms Y M, van Gelderen E M, Batink H D, Timmermans P B, van Zwieten P A
Life Sci. 1983 Mar 28;32(13):1499-505. doi: 10.1016/0024-3205(83)90916-5.
For a series of 12 serotonin antagonists, largely varying in potency, the decrease in diastolic pressure was determined after intravenous injection into pentobarbitone-anaesthetized normotensive rats. The hypotensive activity of these antagonists was correlated with their affinity for alpha 1-adrenoceptors, established by [3H]prazosin radioligand displacement, and the 5-HT2 serotonergic receptor, determined by inhibition of specific [3H]mianserin binding. The radioligand binding assays were performed since they correspond to the in vivo antagonistic potencies of the antagonists at alpha 1--and 5-HT2-receptors, respectively. A close correlation (r = 0.963) was found between the affinity for alpha 1-adrenoceptors and hypotensive activity. On the other hand, a negative correlation of lower statistical quality (r = -0.808) existed between the affinity for 5-HT2-receptors and the depressor potency. In this series of 12 compounds, the new antihypertensive drug ketanserin is included for which it has been speculated that it lowers blood pressure by virtue of its serotonin antagonistic activity. The results of the present study, however, point towards alpha 1-adrenolytic potency as an important mechanism in the hypotensive action of the drug.
对于一系列12种效力差异很大的5-羟色胺拮抗剂，在静脉注射到戊巴比妥麻醉的正常血压大鼠体内后，测定舒张压的降低情况。这些拮抗剂的降压活性与其对α1肾上腺素能受体的亲和力相关，该亲和力通过[3H]哌唑嗪放射性配体置换法确定，以及与5-HT2血清素能受体的亲和力相关，该亲和力通过抑制特异性[3H]米安色林结合来测定。进行放射性配体结合试验是因为它们分别对应于拮抗剂在α1和5-HT2受体处的体内拮抗效力。在对α1肾上腺素能受体的亲和力和降压活性之间发现了密切的相关性（r = 0.963）。另一方面，在对5-HT2受体的亲和力和降压效力之间存在较低统计学质量的负相关性（r = -0.808）。在这12种化合物系列中，包含了新的抗高血压药物酮色林，据推测它凭借其5-羟色胺拮抗活性降低血压。然而，本研究结果表明α1肾上腺素能阻断效力是该药物降压作用的重要机制。
