Synthesis with Improved Yield and Study on the Analgesic Effect of 2‐Hydroxyphencyclidine.

Solati

Hajikhani

et al. 2011

Self Cite

Phencyclidine (1-(1-phenylcyclohexyl) piperidine, CAS 956-90-1, PCP, I) and its derivatives have shown many analgesic effects. In this research, a new derivative of PCP (1-[1-(2-methylphenyl) (cyclohexyl)l3-piperidinol, PD, II) was synthesized and its analgesic (acute and chronic pains) effects were examined on rats 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 are compared to PCP and control groups. The results indicated that II produces higher analgesic effects in the tail immersion test compared to the PCP and control groups, with a marked and significant increase in tail immersion latency for the doses 1, 5 and 10 mg/kg. The formalin test showed that PD (II) is not effective in acute chemical pain (phase I, 0-5 min after injection) in all doses but chronic pain (initial-phase II, 15-40 min after injection) is significantly attenuated by this compound compared to PCP and saline (control) in dosesof 5 and 10 mg/kg. It is concluded that II is effective in acute thermal (in all doses) and chronic (doses of 5 and 10 mg/kg) pains; however, it is not effective in acute chemical pain compared to PCP and control.

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Synthesis and analgesic effects of 1-[1-(2-methylphenyl)(cyclohexyl)]-3-piperidinol as a new derivative of phencyclidine in mice

Solati

Hajikhani

et al. 2011

Self Cite

“…Spectroscopic data (IR, 1 H and 13 C-NMR, mass spectrometry) confirmed the structures of all reported com- Because 2-hydroxy-1-phenyl-cyclohexyl piperidine (2-OH-PCP, another analogue of the phencyclidine family) has a hydrophilic structure and the concentration of this compound in the aqueous phase is greater than in the lipid phase. It has a rapid analgesic effect on acute and phasic pain [11] and even better analgesic effects in the tail-flick latencies in comparison with ketamine (another famous drug in this family with the same effects) [14]. Therefore, we used α-tetralone with an extra conjugated aromatic ring and with an one hydroxy group on the cyclohexane ring, which is predicted to increase the mentioned analgesic effects and the other drug effects compared with those of phencyclidine (PCP).…”

Section: Resultsmentioning

confidence: 99%

“…But 2-OH-PCP has a hydrophilic structure, therefore, the concentration of this drug in the aqueous phase is greater than in the lipid phase, and the analgesic properties of this drug might result from open-channel block impeding ionic flow. This may explain why 2-OH-PCP has a rapid analgesic effect in comparison with ketamine on acute and phasic pain [14]. The acute analgesic effect of ketamine is closely associated with sensory and locomotor side effects.…”

Section: Discussionmentioning

confidence: 99%

“…Since a hydroxy group has been added to position 2 of the cyclohexane ring of PCP (2-OH-PCP), this compound is more hydrophilic than PCP and has previously been synthesized with low yield [11], and higher yield recently [14], and the analgesic effect of this compound was compared with that of ketamine (another PCP analogue, Scheme 1) [14]. Ketamine in low sub-anaesthetic doses is reliable as an analgesic in acute pain [15].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis and Biological Properties of 2-Hydroxy-1-(1-phenyltetralyl)piperidine and Some of its Intermediates as Derivatives of Phencyclidine

Mahmoudi

2011

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Phencyclidine (1-(1-phenylcyclohexyl)piperidine, CAS 956-90-1, PCP) has shown analgesic effects. Some of its derivatives were synthesized and their biological properties were studied. To date, only saturated ketones have been used as starting materials for synthesizing the phencyclidine family. In order to show desirable biological activity, the aromatic and piperidine rings are necessary for these compounds. Using alpha-tetralone as a starting material, 2-hydroxy-1-(-phenyltetralyl)piperidine, an analogue of the phencyclidine family, and some of its intermediates were synthesized. This ketone was reacted with phenyl magnesium bromide and the resultant alcohol was reacted with acetic anhydride to give alkene that was treated with potassium permanganate to give diol. This compound was treated with a suspension of sodium azide and trichloroacetic acid to give the azide compound that was reduced with LiAlH4 to give the primary amine. Cyclization of this compound with 1,5-dibromopentane finally gave a tertiary amine. It is predicted that the title compound 2-hydroxy-1-(1-phenyltetralyl)piperidine exerts a potent analgesic effect on acute and phasic pain.

Synthesis and analgesic effects of new pyrrole derivatives of phencyclidine in mice

Solati

Hajikhani

et al. 2011

Self Cite

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.