Synthesis and determination of acute and chronic pain activities of 1-[1-(3-methylphenyl) (tetralyl)]piperidine as a new derivative of phencyclidine via tail immersion and formalin tests

Abstract

Phencyclidine (1-(1-phenylcyclohexyl)piperidine, CAS 956-90-1, PCP, 1) and ketamine (2-O-chlorophenyl-2-methylaminocyclohexan, CAS 1867-66-9, II) revealed some analgesic effects. Some of their derivatives have been synthesized for biological properties studies. Utilizing 1-tetralone as a starting material, 1-[1-(3-methylphenyl)(tetralyl)]piperidine, (PCP-CH3-tetralyl, III) was synthesized and its analgesic effects were studied on rats via tail immersion (as a model of acute thermal pain) and formalin (as a model of acute chemical and chronic pain) tests and compared with those of ketamine and PCP. The results indicated a marked anti-nociception 2-25 min after ketamine injection, but this analgesic effect lasted for 40 min following PCP-CH3-tetralyl application in the tail immersion test. However, the data obtained from the formalin test showed that chronic pain could be significantly attenuated by ketamine, PCP and PCP-CH3-tetralyl.

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

“…Thisw ill beunderstood ass uccessfuland satisfactory treatmentof pain. Suchtreatments arep resented in avast numberof scientificworksw hichh ave recentlyappeared in the field of applied analgesicor fundamentalresearchintonociception [1].Forexample, phencyclidine (1-(1-phenylcyclohexyl)piperidine,C AS 956-90-1,P CP, I ,S cheme 1) derivativesexhibiting analgesica ctivity arewell knownfort hispurpose [2][3][4][5][6][7][8][9].…”

“…n Acuteand chronicpain n Analgesics n CAS 956-90-1 n Formalin test n Phencyclidine,derivative n Tail immersion test wasprepared and its analgesiceffects weree xamined on rats using tail immersion (asamodel of acutethermalpain) and formalin (asamodel of acuteand chronic chemicalpain) tests.The results arecompared withPCP and control groups.Asindicated in our previous work on thisfamily [4,6,8,9], incorporation of amethyl grouponthe aromaticring of the molecule will generate pronounced effects on electron distribution and dipole moments becauseo fi ts high electron donating character [14].Inaddition,incorporation of ahydroxylg roup on the piperidine ring of the molecule wasanticipated tohavepronounced effects on its hydrophilicproperties [3,15]and increasesthe polarity and solubility activities of the drug.…”

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

“…Inthe presents tudy,twon ewpyrrole derivativesof PCP withchangesin substitution on PCP'sphenyl groupand replacing the piperidine witharomaticpyrrole ringsweresynthesized. Asindicated in our previous worko nsubstitution of the methylgroup(high electron donating groupwithm oree lectron distribution and dipole moment), methylphenyl( tolyl) insteado fp henylgroupgeneratesstrongeranalgesiceffects [7,8].Inaddition because of the existenceo fp harmacological propertiesof pyrrole derivatives [10,11]and investigation on substituting aromaticpyrrole insteado fn onaromaticpiperidine group,suchn ewly developed changesw ereselected in our work. The results indicated that substitution of pyrrole insteado fp iperidine decreased the analgesiceffects of thisnewdrug( II)d ueto sharing of the non-bonding nitrogen electronsof pyrrole in the aromatic ring aswell asdecreasing the hydrophilicpropertiesof thisatom and drug( II).…”

“…Ithasbeen observed from our previous work [5][6][7][8] thatsubstituting amethylgroup(withhigh electron distribution and dipole moments [9])o nthe phenylring cani mpart higheranalgesiceffects in the synthesized drugs.Thereforethisgroupwasalsoadded too ur new and initiallys ynthesized drug( I )top roduceasecond compound ( III).…”

“…Thereforei ts eemst hatt he substitution of the aromaticpyrrole ring insteadofthe non-aromaticpiperidine ring initiated the reduction of analgesiceffects of the drug( II). Strong electron donating propertiesof the methylg roupo n para position of the phenylring facilitatethe binding tothe NMDA receptorcomplexand will beable toi ncreasetail immersion latenciesin comparison withthe othergroups,a sr eported in our previous work [7,8].The differencei nthe tail immersion latenciesw asevaluated using analysisof variancem ethod (ANOVA). The drugs( I-III)and DMSO (control) wereadministered intraperitoneallyw iththe doseo f1 mg/kg, 30 min priort of ormaldehyde injection.…”