Synthesis and determination of acute and chronic pain activities of 1-[1-(4-methylphenyl)(cyclohexyl)] morpholine as a new phencyclidine derivative in rats

Abstract

Phencyclidine (1-(1-phenylcyclohexyl)piperidine, CAS 77-10-1, PCP, I) and many of its analogues have been synthesized and their pharmacological properties studied. In this research, new methyl morpholine derivative of phencyclidine (1-[1-(4-methylphenyl) (cyclohexyl)]morpholine, Methyl-PCM, III) was synthesized and the acute and chronic pain activities were studied using tail immersion and formalin tests on rats and compared to PCP and PCM (1-(1-phenylcyclohexyl)morpholine, CAS 2201-40-3, PCP-morpholine, II). The results Indicated that Methyl-PCM (III, 6 mg/kg, i.p) produces more analgesic effects in tail immersion test (as a model of acute thermal pain) in comparison with the PCP, PCM and control groups. Meanwhile, this analgesic effect was markedly shown 5-15 min after the compound III application. In formalin test analysis, the acute pain (phase I) could not be affected by any drugs, but the chronic formalin pain (phase II) could be diminished by PCM and especially compound III. The chronic analgesic effect of Methyl-PCM was markedly shown in the late phase of chronic pain.

Recyclization of Maleimides by Binucleophiles as a General Approach for Building Hydrogenated Heterocyclic Systems

“…The reactions of maleimides with the involvement of 1,4-N,O-binucleophiles also proceed in a similar way. During these transformations, unsaturated oxazine (morpholine) cycles are formed, which are part of a number of compounds with a wide spectrum of biological activity [52][53][54][55][56][57][58][59][60][61][62][63][64][65][66]. A. V. Zorina et al [67,68] studied the interaction of 1 with aminophenol 55 and aminoethanols 56 in detail.…”

Synthesis and Antinociceptive Behaviors of New Methyl and Hydroxyl Derivatives of Phencyclidine

“…Therefore, the glutamate receptor antagonists, particularly the NMDA receptor antagonists, are amongst important agents in controlling various types of pain [6]. Recently, several PCP derivatives (with substitution changes in the molecule) have been synthesized and their pharmacological activities have been tested [7][8][9][10][11][12][13]. Revealed in the previous works [8-10, 12, 13] on this family of compounds, the incorporation of methyl group to the aromatic ring of the molecule generates pronounced effects on electron distribution and dipole moments because of its high electron donating character [14].…”