title: Synthesis and analgesic effects of new pyrrole derivatives of phencyclidine in mice.
abstract: Phencyclidine (1-(1-phenylcyclohexyl)piperidine, CAS 956-90-1, PCP, I) and many of its analogues have shown some pharmacological effects. In this study, new pyrrole derivatives of I (1-(1-phenylcyclohexyl)pyrrole, II and 1-[1-(4-methylphenyl)(cyclohexyl)]pyrrole, III) and their intermediates were synthesized and the acute and chronic pains were examined on mice using tail immersion (as a model of acute thermal pain) and formalin (as a model of acute and chronic chemical pain) tests and the results were compared with the PCP and control groups. The results indicated that III generated higher analgesic effects in the tail immersion test compared to the PCP and control (dimethyl sulfoxide, DMSO) groups, demonstrating a marked and significant increase in tail immersion latency, but this effect was not observed for II in the dose of 1 mg/kg. The formalin test showed that III was effective in acute chemical pain (phase I, 0-5 min after injection), but was not effective for II at the same dosage compared to the PCP and control groups. Also chronic pain will be significantly attenuated by III but II was not effective as compared to the other groups. It is concluded that substitution of the aromatic pyrrole ring instead of piperidine in the PCP molecule will not be effective alone in tail immersion and formalin tests but the addition of a methyl group (with high electron donating and dipole moments) on the phenyl group plus substitution of the aromatic pyrrole ring can be effective in acute and chronic pain compared to the PCP and control groups.
authors.affiliation: Department of Chemistry, Faculty of Science, Islamic Azad University, Karaj branch, Karaj, Iran. a-ahmadi@kiau.ac.ir
authors.forename: Abbas
authors.initials: A
authors.lastname: Ahmadi
authors.forename: Jalal
authors.initials: J
authors.lastname: Solati
authors.forename: Ramin
authors.initials: R
authors.lastname: Hajikhani
authors.forename: Sara
authors.initials: S
authors.lastname: Pakzad
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D002908:Chronic Disease; D004121:Dimethyl Sulfoxide; D005557:Formaldehyde; D006358:Hot Temperature; D007202:Indicators and Reagents; D008745:Methylation; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D007202:Indicators and Reagents; D011758:Pyrroles; D005557:Formaldehyde; D010622:Phencyclidine; D004121:Dimethyl Sulfoxide