Kramer M S, Cutler N, Feighner J, Shrivastava R, Carman J, Sramek J J, Reines S A, Liu G, Snavely D, Wyatt-Knowles E, Hale J J, Mills S G, MacCoss M, Swain C J, Harrison T, Hill R G, Hefti F, Scolnick E M, Cascieri M A, Chicchi G G, Sadowski S, Williams A R, Hewson L, Smith D, Carlson E J, Hargreaves R J, Rupniak N M
Merck Research Laboratories, West Point, PA 19456, USA.
Science. 1998 Sep 11;281(5383):1640-5. doi: 10.1126/science.281.5383.1640.
The localization of substance P in brain regions that coordinate stress responses and receive convergent monoaminergic innervation suggested that substance P antagonists might have psychotherapeutic properties. Like clinically used antidepressant and anxiolytic drugs, substance P antagonists suppressed isolation-induced vocalizations in guinea pigs. In a placebo-controlled trial in patients with moderate to severe major depression, robust antidepressant effects of the substance P antagonist MK-869 were consistently observed. In preclinical studies, substance P antagonists did not interact with monoamine systems in the manner seen with established antidepressant drugs. These findings suggest that substance P may play an important role in psychiatric disorders.
P物质在协调应激反应并接受单胺能神经纤维汇聚性支配的脑区中的定位表明，P物质拮抗剂可能具有心理治疗特性。与临床使用的抗抑郁药和抗焦虑药一样，P物质拮抗剂可抑制豚鼠的隔离诱导发声。在一项针对中度至重度重度抑郁症患者的安慰剂对照试验中，持续观察到P物质拮抗剂MK - 869具有显著的抗抑郁作用。在临床前研究中，P物质拮抗剂并未以已确立的抗抑郁药的作用方式与单胺系统相互作用。这些发现表明，P物质可能在精神疾病中起重要作用。
