Kovács G L, Nyolczas N, Kriván M, Gulya K
Institute of Pathophysiology, University Medical School, Szeged, Hungary.
Eur J Pharmacol. 1988 Jun 10;150(3):347-53. doi: 10.1016/0014-2999(88)90017-9.
The novel and highly selective, conformationally restricted enkephalin analogue for delta-opioid receptors, [D-Pen2,D-Pen5]enkephalin (DPDPE; Pen = penicillamine), was studied in various in vivo tests for analgesia, tolerance and physical dependence. Intracerebroventricular (i.c.v.) administration of DPDPE caused a dose-dependent, naloxone-reversible antinociception, measured with the heat-irradiant (tail-flick) method. Acute tolerance developed to the antinociceptive effect of DPDPE. DPDPE also caused mild signs of physical dependence (withdrawal hypothermia and body weight loss) after repeated peptide treatment. Severe signs of morphine withdrawal (e.g. withdrawal jumping) on the other hand, could not be reversed by the administration of DPDPE. It is concluded that the activation of central delta-opioid receptors may play a role in controlling pain mechanisms, and that this activation is followed by the rapid development of a tolerance to this action.
新型且高度选择性的、构象受限的δ-阿片受体脑啡肽类似物[D-青霉胺2，D-青霉胺5]脑啡肽（DPDPE；青霉胺=penicillamine）在多种体内镇痛、耐受性和身体依赖性试验中进行了研究。采用热辐射（甩尾）法测量，脑室内（i.c.v.）给予DPDPE可引起剂量依赖性、纳洛酮可逆的抗伤害感受作用。对DPDPE的抗伤害感受作用产生了急性耐受性。在重复给予该肽后，DPDPE还引起了轻度的身体依赖性体征（戒断性体温过低和体重减轻）。另一方面，给予DPDPE不能逆转吗啡戒断的严重体征（如戒断跳跃）。得出的结论是，中枢δ-阿片受体的激活可能在控制疼痛机制中起作用，并且这种激活之后会迅速对该作用产生耐受性。
