Department of Chemistry, Faculty of Science, Islamic Azad University, Karaj Branch, P.O. Box: 31485- 313, Karaj, Iran.
Mini Rev Med Chem. 2014 Jan;14(1):64-71. doi: 10.2174/1389557513666131119203551.
Phencyclidine (PCP, I) and many of its derivatives have demonstrated many pharmacological effects. They interact with a number of neurotransmitter systems within the central nervous system. For example, Phencyclidine is a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) subtype of the glutamate receptor, and it causes the release and inhibits the reuptake of monoaminergic neurotransmitters, including dopamine, serotonin and norepinephrine. In this study, new thienyl (TCP, II), as well as benzothiophen (BTCP, III) derivatives (IV-VII) were synthesized. The acute and chronic pain activities of these drugs were studied using the tail immersion and formalin tests on mice and the results were compared with PCP, TCP and control groups at dosage of 10 mg/kg. The results indicated that the drug VII produced more analgesic effects on acute chemical pain in formalin test compared with other drugs. In addition, this analgesic effect was remarkably seen for drugs II, VI and VII in chronic pain in the mentioned test in comparison with other drugs. Also, the results showed that acute thermal pain could be diminished by drugs VI, II and I compared with other drugs in tail immersion test. It can be concluded that more analgesic effects of new BTCP analogues (VI and VII) may be concerned with antinociception activities of benzothiophene group and also with binding to cocaine site on the dopamine transporter receptor which seems to be more potent than PCP receptor in decreasing pain.
苯环利定（PCP，I）及其许多衍生物表现出许多药理学作用。它们与中枢神经系统内的许多神经递质系统相互作用。例如，苯环利定是非竞争性 N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体拮抗剂，它导致单胺能神经递质的释放和抑制再摄取，包括多巴胺、血清素和去甲肾上腺素。在这项研究中，合成了新的噻吩基（TCP，II）以及苯并噻吩基（BTCP，III）衍生物（IV-VII）。在小鼠的尾部浸入和福马林试验中研究了这些药物的急性和慢性疼痛活性，并将结果与 PCP、TCP 和对照组在 10mg/kg 剂量下进行了比较。结果表明，与其他药物相比，药物 VII 在福马林试验中对急性化学疼痛具有更强的镇痛作用。此外，与其他药物相比，在所述试验的慢性疼痛中，药物 II、VI 和 VII 产生了更明显的镇痛作用。此外，结果表明，与其他药物相比，药物 VI、II 和 I 可减轻尾部浸入试验中的急性热痛。可以得出结论，新的 BTCP 类似物（VI 和 VII）具有更强的镇痛作用，可能与苯并噻吩基团的镇痛作用以及与多巴胺转运体受体上的可卡因结合位点有关，这似乎比 PCP 受体更能减轻疼痛。
