France C.P., Woods J.H.
Departments of Pharmacology and Psychology, University of Michigan, Ann Arbor, MI 48109, USA.
Behav Pharmacol. 1992 Apr;3(2):133-141.
Naloxone benzoylhydrazone (NalBzoH) has been suggested to be a selective opioid agonist, exerting its effects through the kappa(3) subtype of opioid receptor. In the present experiments NalBzoH was studied for its discriminative stimulus, analgesic, and respiratory effects in rhesus monkeys. Up to the largest doses administered (1.0-3.2mg/kg), NalBzoH failed to substitute for the discriminative stimulus effects of the kappa agonist ethylketocyclazocine or those of the µ agonist alfentanil. However, in morphine-treated (3.2mg/kg/day) monkeys NalBzoH substituted completely for the discriminative stimulus effects of the opioid antagonist naltrexone. NalBzoH antagonized the discriminative stimulus effects of alfentanil in morphine-treated subjects and, at larger doses, antagonized the discriminative stimulus effects of ethylketocyclazocine. NalBzoH did not produce analgesic effects and had only modest effects on respiration. However, NalBzoH antagonized the analgesic effects as well as the respiratory-depressant effects of alfentanil; at doses 10-15 times larger than those that antagonized alfentanil, NalBzoH also antagonized analgesic effects of the kappa agonist U-50,488. For both µ and kappa agonists, NalBzoH was slightly more potent in antagonizing discriminative stimulus effects as compared to analgesic effects. Thus, NalBzoH is a µ-selective opioid antagonist in rhesus monkeys and is equipotent to naloxone in antagonizing alfentanil. While demonstrating µ-selective antagonism, the current study fails to provide support for the proposed kappa agonist actions of NalBzoH.
纳洛酮苯甲酰腙（NalBzoH）被认为是一种选择性阿片类激动剂，通过阿片受体的κ(3)亚型发挥作用。在本实验中，对NalBzoH在恒河猴中的辨别刺激、镇痛和呼吸作用进行了研究。在给予的最大剂量（1.0 - 3.2mg/kg）范围内，NalBzoH未能替代κ激动剂乙基酮环唑新或μ激动剂阿芬太尼的辨别刺激作用。然而，在吗啡治疗（3.2mg/kg/天）的猴子中，NalBzoH完全替代了阿片类拮抗剂纳曲酮的辨别刺激作用。NalBzoH拮抗了吗啡治疗的受试者中阿芬太尼的辨别刺激作用，并且在较大剂量时，拮抗了乙基酮环唑新的辨别刺激作用。NalBzoH没有产生镇痛作用，对呼吸只有适度影响。然而，NalBzoH拮抗了阿芬太尼的镇痛作用以及呼吸抑制作用；在比拮抗阿芬太尼的剂量大10 - 15倍时，NalBzoH也拮抗了κ激动剂U - 50,488的镇痛作用。对于μ和κ激动剂，与镇痛作用相比，NalBzoH在拮抗辨别刺激作用方面的效力略强。因此，NalBzoH在恒河猴中是一种μ选择性阿片类拮抗剂，在拮抗阿芬太尼方面与纳洛酮等效。虽然证明了μ选择性拮抗作用，但目前的研究未能为所提出的NalBzoH的κ激动剂作用提供支持。
