Koyuncuoğlu H, Güngör M, Sağduyu H, Aricioğlu F
Department of Pharmacology and Clinical Pharmacology, Istanbul Medical Faculty, Turkey.
Pharmacol Biochem Behav. 1990 Apr;35(4):829-32. doi: 10.1016/0091-3057(90)90366-p.
The development of physical dependence on opiates appears to involve an inhibition by opiates of L-asparaginase and glutaminase, and the blockade by opiates of aspartatergic (ASPergic)/glutamatergic (GLUergic) receptors. Ketamine (K) (0.5 or 1 mg/kg) or dextromethorphan (DM) (1 or 2 mg/kg), both of which are known to decrease the responsiveness of ASPergic/GLUergic receptors, were administered to the three morphine (M)-containing pellets implanted rats prior to 2 mg/kg naloxone (NL) injection. Whereas 0.5 mg/kg K showed no significant effect on abstinence syndrome signs, 1 mg/kg K and 1 mg/kg DM significantly attenuated some of the signs. The attenuation or prevention of all the signs were observed after 2 mg/kg DM administration. Almost complete prevention was seen from the second minute on during the ten-minute observation period. As ASP and GLU antagonists K and DM have this antagonizing effect on the precipitated abstinence syndrome signs, the manifestation of abstinence syndrome may mainly result from the normalization of ASP and GLU production because of the disinhibition by NL of the enzymes and the stronger stimulation of ASPergic/GLUergic receptors which have no opiate blockade after NL injection.
对阿片类药物产生身体依赖性的发展似乎涉及阿片类药物对L-天冬酰胺酶和谷氨酰胺酶的抑制，以及阿片类药物对天冬氨酸能/谷氨酸能（ASPergic/GLUergic）受体的阻断。氯胺酮（K）（0.5或1毫克/千克）或右美沙芬（DM）（1或2毫克/千克），已知二者均可降低ASPergic/GLUergic受体的反应性，在向植入含吗啡（M）丸剂的大鼠注射2毫克/千克纳洛酮（NL）之前给予这两种药物。虽然0.5毫克/千克的K对戒断综合征体征没有显著影响，但1毫克/千克的K和1毫克/千克的DM可显著减轻部分体征。给予2毫克/千克的DM后，观察到所有体征均有减轻或预防作用。在十分钟的观察期内，从第二分钟开始几乎观察到完全预防作用。由于ASP和GLU拮抗剂K和DM对诱发的戒断综合征体征有这种拮抗作用，戒断综合征的表现可能主要是由于NL对酶的去抑制作用以及对ASPergic/GLUergic受体的更强刺激导致ASP和GLU产生恢复正常所致，NL注射后这些受体不再有阿片类药物的阻断作用。
