CARDIOVASCULAR PROPERTIES OF 5-HT 1 RECEPTOR AGONISTS

5-HT1受体激动剂是有效的长效剂，可降低 对猫、狗和大鼠的动脉压和诱发心动过缓。 8-羟基-2-二正丙氨基四氢呋喃(8-OH DPAT)将作为 并与新合成的化合物进行比较。 10-羟基取代的阿朴吗啡衍生物 具有CH3、CH2OH、H等，以及改变取代 氮气(阿朴吗啡)。初步研究表明， 10-CH3，N-CH3阿朴吗啡衍生物与 行为和心血管改变--由8-羟基DPAT，a 选择性5-HT1a受体激动剂。阿朴吗啡化合物具有 不与DA2受体相互作用，我们的假设是烷基 阿朴吗啡10位上的取代引入强效 5-HT1受体激动剂的特性。 实验程序将评估可能的中央和 低血压和心动过缓反应的外周部位 由这一系列化合物诱导，调查反射 交感神经和副交感神经的激活 系统，并选择性和特异性地确定受体使用 各种放射性配基结合和生物测定程序。 本研究的直接目标包括：(1)确定5- 用于心血管系统控制的HT1受体，(2) 评估目前的假设是，这些药物是有效的5-羟色胺- 受体激动剂，这两个系列的药物都非常 有效阻断双侧颈动脉的心血管反应 闭塞，引起心动过缓和低血压，(3)识别 5-羟色胺受体亚型的激动剂；这当然是必要的 以帮助确定该受体的生理作用，以及(4)由于我们 没有选择性的5-HT1受体拮抗剂，一种活性 显然需要药物，这项研究将确定拮抗剂 5-HT1受体亚型。 这项研究将把化学实验和生物实验结合起来 促进我们对5-HT1作用的理解的程序 心血管药理学中的受体。

5-HT1-receptor agonists are potent, long acting agents that lower arterial pressure and induce bradycardia in cats, dogs, and rats. 8-OH-2-di-n propylaminotetralin (8-OH DPAT) will serve as the reference chemical and will be compared with newly-synthesized apomorphine derivatives in which the 10-OH group is substituted with CH3, CH2OH, H, etc., as well as altering substitution on nitrogen (aporphines). Preliminary studies ahve demonstrated that the 10-CH3, N-CH3 aporphine derivative parallels closely the behavorial and cardiovascular changes-induced by 8-OH DPAT, a selective 5-HT1A receptor agonist. The aporphine compound has no interaction with DA2-receptors and our hypothesis is that alkyl substitutions in the 10-position of apomorphine introduce potent 5-HT1-receptor agonist properties. The experimental procedures will evaluate possible central and peripheral sites for the hypotensive and bradycardic responses induced by these series of compounds, investigate reflex activations of the sympathetic and parasympathetic nervous systems, and determine receptor selectively and specificity using various radioligand binding and bioassay procedures. Direct goals of this research include: (1) determine the role of 5- HT1 -receptors for control of the cardiovascular system, (2) evaluate present hypothesis is that these agents are potent 5-HT- receptor agonists, and both of these series of agents are very potent in blocking cardiovascular responses to bilateral carotid occlusion, inducing bradycardia and hypotension, (3) identifying agonists for serotonin-receptor subtypes; this is certainly needed to help define physiological roles of this receptor, and (4) since we have no selective antagonists for 5-HT1 receptors, an active agent is clearly needed and this research will identify antagonists for 5-HT1 receptor subtypes. This research will combine chemical and biological experimental procedures to advance our understanding of the role of 5-HT1 receptors in cardiovascular pharmacology.