Yocca F D
CNS Pharmacology, Bristol-Myers Squibb Company, Wallingford, CT 06492-7660.
J Clin Psychopharmacol. 1990 Jun;10(3 Suppl):6S-12S. doi: 10.1097/00004714-199006001-00003.
Preclinical neurochemical studies indicate that buspirone and gepirone bind selectively to presynaptic (dorsal raphe) and postsynaptic (hippocampus, cortex) 5-hydroxytryptamine1A (5-HT1A) receptor binding sites. Furthermore, in functional neurochemical and electrophysiologic receptor studies, azapirones in general display partial agonist activity at postsynaptic 5-HT1A receptors linked negatively to adenyl cyclase and appear to demonstrate a similar profile on hippocampal CA1 pyramidal neurons sensitive to the effects of 5-HT. Through their action at presynaptic 5-HT1A receptors, these agents have been shown to dose-dependently inhibit cortical and hippocampal 5-HT synthesis while inhibiting the firing of 5-HT--containing dorsal raphe neurons, both in vitro and in vivo. These results suggest that the efficacy seen in clinical trials of anxiety and depression may be related to buspirone's and gepirone's complex interaction with presynaptic and postsynaptic 5-HT1A receptors, which initiate long-term changes in central 5-HT neurotransmission.
临床前神经化学研究表明，丁螺环酮和吉哌隆可选择性地与突触前（中缝背核）和突触后（海马、皮质）5-羟色胺1A（5-HT1A）受体结合位点结合。此外，在功能性神经化学和电生理受体研究中，氮杂螺环酮类药物总体上在与腺苷酸环化酶负相关的突触后5-HT1A受体上表现出部分激动剂活性，并且在对5-羟色胺作用敏感的海马CA1锥体神经元上似乎也表现出类似的特征。通过作用于突触前5-HT1A受体，已证明这些药物在体外和体内均能剂量依赖性地抑制皮质和海马5-羟色胺的合成，同时抑制含5-羟色胺的中缝背核神经元的放电。这些结果表明，在焦虑和抑郁临床试验中所观察到的疗效可能与丁螺环酮和吉哌隆与突触前和突触后5-HT1A受体的复杂相互作用有关，这种相互作用会引发中枢5-羟色胺神经传递的长期变化。
