Houde R W
Br J Clin Pharmacol. 1979;7 Suppl 3(Suppl 3):297S-308S. doi: 10.1111/j.1365-2125.1979.tb04704.x.
Two fundamentally different types of narcotic-antogonists have been found to be very effective analgesics with relatively low dependence-producing potentials. These two drug classes can be distinguished as being either morphine-like or nalorphine-like on the basis of their subjective and objective effects after single doses and on chronic administration, and by the character of their abstinence syndromes on abrupt withdrawal or on precipitation by other antagonists. To explain differences in side effects associated with their analgesic actions, the existence of three types of receptors has been postulated: a μ receptor which is believed to be associated with euphoria and other typical morphine-like effects and a kappa (χ) and a sigma (σ) receptor which are believed to be associated with the sedative and psychotomimetic effects, respectively, of the nalorphine-like drugs. The antagonist-analgesics of the morphine-type have the characteristics of being agonists of low intrinsic activity but with high affinity for the μ receptor. Representative analgesics of this type are profadol, propiram and buprenorphine. The antagonist-analgesics of the nalorphine-type are drugs which are believed to have varying degrees of affinity and intrinsic activity at all three receptors, but characteristically seem to act merely as competitive antagonists with no intrinsic activity at the μ receptor. Representative analgesics of this type are pentazocine, nalbuphine and butorphanol. There are considerable differences among the individual drugs of each type in terms of their analgesic and narcotic-antagonistic potencies. However, clear differences in analgesic efficacy among any of the antagonist-analgesics remain to be proved. All give evidence of being capable of relieving pain in nondependent patients in situations in which doses of morphine (or its surrogates) usually used would be effective. The major advantages of the partial agonists of the morphine-type over the nalorphine-type drugs are that they have not been found to produce psychotomimetic reactions, and they seem to have fewer potentially deleterious effects in cardiac patients.
已发现两种根本不同类型的麻醉拮抗剂是非常有效的镇痛药，产生依赖性的可能性相对较低。根据单次给药和长期给药后的主观和客观效果，以及突然停药或被其他拮抗剂激发时戒断综合征的特征，这两类药物可区分为吗啡样或烯丙吗啡样。为了解释与其镇痛作用相关的副作用差异，人们推测存在三种类型的受体：μ受体，被认为与欣快感及其他典型的吗啡样效应有关；κ（χ）受体和σ受体，分别被认为与烯丙吗啡样药物的镇静和拟精神病效应有关。吗啡型拮抗镇痛药的特点是内在活性低但对μ受体亲和力高的激动剂。这类代表性的镇痛药有普罗法朵、丙哌利定和丁丙诺啡。烯丙吗啡型拮抗镇痛药被认为对所有三种受体都有不同程度的亲和力和内在活性，但通常仅表现为竞争性拮抗剂，对μ受体无内在活性。这类代表性的镇痛药有喷他佐辛、纳布啡和布托啡诺。每种类型的个别药物在镇痛和麻醉拮抗效力方面存在相当大的差异。然而，任何一种拮抗镇痛药在镇痛效果上的明显差异仍有待证实。在通常使用的吗啡（或其替代物）剂量有效的情况下，所有这些药物都证明能够缓解非依赖性患者的疼痛。吗啡型部分激动剂相对于烯丙吗啡型药物的主要优点是，尚未发现它们会产生拟精神病反应，而且它们对心脏病患者似乎具有较少的潜在有害影响。
