Vonvoigtlander P F, Lewis R A, Neff G L, Triezenberg H J
Prog Neuropsychopharmacol Biol Psychiatry. 1983;7(4-6):651-6. doi: 10.1016/0278-5846(83)90040-4.
The analgesic activity of the kappa opioid agonist, U-50,488H, was markedly antagonized by pretreatment with reserpine, p-chlorophenylalanine, and ketanserin. Likewise, analgesic doses of U-50,488H enhance serotonin metabolism. These results suggest that kappa analgesia requires serotonin acting through 5-HT2 receptors. The non-opioid analgesic, nefopam HCl, though a blocker of biogenic amine uptake, displays an analgesic spectrum of action more similar to that of amphetamine than that of the tricyclic antidepressants or serotonin uptake blockers. Likewise p-chlorophenylalanine and ketanserin do not block nefopam analgesia nor do naloxone, atropine, yohimbine, propranolol or haloperidol. However, as reserpine does block nefopam analgesia, biogenic amines acting at other receptors may be involved. The observation that m-tyrosine causes behavioral effects similar to high doses of nefopam suggested that they might be acting through similar mechanisms. However, although m-tyrosine causes analgesia, it is blocked by yohimbine. This suggests that alpha2-adrenoreceptors are involved in m-tyrosine analgesia and that it differs in mechanism from nefopam analgesia.
κ阿片受体激动剂U - 50,488H的镇痛活性，在预先使用利血平、对氯苯丙氨酸和酮色林后被显著拮抗。同样，U - 50,488H的镇痛剂量会增强血清素代谢。这些结果表明，κ阿片受体介导的镇痛作用需要血清素通过5 - HT2受体发挥作用。非阿片类镇痛药盐酸奈福泮虽然是生物胺摄取的阻断剂，但其镇痛作用谱与苯丙胺更相似，而与三环类抗抑郁药或血清素摄取阻断剂不同。同样，对氯苯丙氨酸和酮色林不会阻断奈福泮的镇痛作用，纳洛酮、阿托品、育亨宾、普萘洛尔或氟哌啶醇也不会。然而，由于利血平确实会阻断奈福泮的镇痛作用，可能涉及作用于其他受体的生物胺。间酪氨酸产生与高剂量奈福泮相似的行为效应这一观察结果表明，它们可能通过相似的机制起作用。然而，尽管间酪氨酸会引起镇痛作用，但它会被育亨宾阻断。这表明α2肾上腺素能受体参与了间酪氨酸的镇痛作用，并且其作用机制与奈福泮的镇痛作用不同。
