Kiang J G, Dewey W L, Wei E T
J Pharmacol Exp Ther. 1983 Jul;226(1):187-91.
Intravenous injection of opiate agonists produces in the rat a precipitous but transient fall in heart rate. This bradycardia, which may be a vagal chemoreflex, appears to originate from peripheral opiate receptors because the onset is faster after injections of morphine into the peripheral circulation than after central injections. The bradycardia is blocked by i.v. administration of tertiary and quaternary naloxone at doses which are not effective centrally. Tolerance develops to morphine bradycardia after s.c. infusions of morphine sulfate (e.g., 74 nmol/hr/rat s.c. for 2 days elevated the morphine ED50 by 22 times), but not after central infusions of morphine at doses which are sufficient to produce physical dependence and tolerance to morphine analgesia. Subcutaneously infused morphine animals are cross-tolerant to FK33,824 (Tyr-D-Ala-Gly-NMePhe-Met(O)-ol), a potent enkephalin analog, and vice versa, but are not tolerant to serotonin or phenyldiguanide. Vagal bradycardia may be a convenient index for studying the peripheral action of opioid agonists.
静脉注射阿片类激动剂会使大鼠心率急剧但短暂下降。这种心动过缓可能是一种迷走神经化学反射，似乎起源于外周阿片受体，因为将吗啡注入外周循环后心动过缓的发作比中枢注射后更快。静脉注射无效剂量的叔胺和季铵纳洛酮可阻断心动过缓。皮下输注硫酸吗啡（例如，74 nmol/小时/大鼠皮下注射2天，使吗啡ED50提高22倍）后，对吗啡心动过缓会产生耐受性，但中枢输注足以产生身体依赖性和对吗啡镇痛耐受性的吗啡剂量后则不会产生耐受性。皮下输注吗啡的动物对强效脑啡肽类似物FK33,824（酪氨酰-D-丙氨酰-甘氨酰-N-甲基苯丙氨酰-甲硫氨酸（O）-醇）具有交叉耐受性，反之亦然，但对5-羟色胺或苯基双胍不产生耐受性。迷走神经心动过缓可能是研究阿片类激动剂外周作用的一个方便指标。
