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1. llE|{POXAMntl, 201I, mo.u26, Np 4' c. I-5 9KCnEPI4MEHTAJIbHLIE PAEOTbI vnK s77 PYRROLE ANALOGUES OF PHENCYCLIDINE DECREASE FOOD AND WATER CONSUMPTION IN MICE @ 2011 r. J. Solatio*,A. Ahmadi', S. Ptkzadb aDepartment of Biotogy, Islamic Azad (Iniversity, Karaj branch, Karaj, Iran bDepartmentof Chemistry, Faculty of Science,Islatnic Azad University,Karaj branch, Karaj' Iran piperidine, PCP, I) and Abstract - Various studieshave shown that Phencyclidine (1-[i-phenylcyclohexyl] new pyrrole deriv- many of its analoguesdemonstratepl-rarmacclogicileffects.In this paper eflects of some pyrroleI, II, and 1-[1-[4-methylphenvl][cyclohexvl]l-pyrroie on food III) atives (l-[1-phelylcyclohexyl] of, *"." inveiiigated.Animals were deprived for 24hbefore initial of each test for food and water intake in and then in l- and warer intake evaluation. pCp ai.rcl derivativeswere injected intraperitoneallv.(i.p.) its -i.L I 80 min post-injection, the treatedgroupswere measuredfor food and water intake, respect- I 2 hour and 30- ofPCP (II and III)' de- iully. The resultsobtained from the presentstudy sliow that the pyrrole derivatives with the vehicle treated control food and water intake in the diprived mice dramaticallyin-comparison crease ;.;irp. O',rr"sultr'srgg.iltnutthepyrro-lederivativesofphenlyilidine(IIandIII)affectthosepartsofceu- tral nervoussystemsthat are involved in feedingbehavior' intake, waterintake, mice' pyrrole derivatives,food Phencyclidine, Kevwortls: ing body weight lossin obeseindividuals, and alsosur- INTRODUCTION gery hasbeen shown to be of useonly in some selected (1-[1-phenylcyclohexyl]piperi- patients, it is clearly recogllized that even moderate Phencyclidine dine, I, PCP Scheme 1) was originally introduced as a weight lossconferssignificant health benefits[9, l0] . with- agent,but it wassubsequently gen".al anesthetic Previousstudiesdemonstratedthat PCP and its an- psycho- irawn fiom usingin humansbecause severe of aloguesalter fbod and water intakc in deprivcd and mimetic sideeffccts[1]. The focus of research PCP on animalslll,12l. Because somephar- of non-deprived hasshiftedfrom its useasan anesthetictowardspoten- macological properties of Pyrrole derivativesaI-rdef- tial applicationsas a lleuropharmaceuticalagentl2l' fectivephysiologic activity of these analogues PCP of PCP prirnarily binds to the N-methyl-D-asparate [13], in the presentstudy,effectsof tl-re new pyrrole de- the conduc- iiuaiiuesof PCP on food and water intakeswere evalLt- (NMDA) receptorcomplex and block-s iance of' NMDA-rnediated gating of the calcium ated. channcl [3, 4]. Howevet various studiesshowedthat diffcrent receptors in the central neryous system such 'as METHODS AND MATERIALS dopaminergic,seretonergic,and nicotinic cholin- ergiciystemsare involvedin the modulation of behav- Preparationsof lhe derivatives ioial eifect of PCP and its analogues. of the above All l-[1-phenylcyclohexyl]piperidine (PCP) I' This mentiotted lleural systemsare main parts of central wis preparedin58% yield from l-piperid- behav- that are involvedin control of different systems "ompb,t.td inocyclohexanecarbonitrile(IV) and phenyl magne- food and water intake [5-8]' iors including sium bromide according to a well-known procedure' Obesity is a health problem that is reaching epi- The lrydrochloride salt of I (m.p- 233-234' C) was with a significant demic proportions and is associated using2-propanoland HCl, and then wasre- pathologic prepared mort,idity rate. Obesity and its associated from 2-propanol[14]. crystallized f'eatures major causes illnessand death world- of are pyrrole (PCP-Pyrrole) II' I -phenylcyclohexyl] wide. In the United States, obesity accouuts for 1- [ This iompound was prepared from 1-pyrrolecyclo- at current rates of in- anntlally, and 280.000deatl-rs (9 and phenyl magnesium bro- it will supplantsmoking asthe primary causeof hexanecarbonitrile relatively few mide according to a known procedure' Tl-rehydro- preventable Oeifn. Considering that and havebeen successful induc- chloride salt ofII was preparedusing 2-propanol in iherapeuticapproaches -."ur", from 2-propanol and then was recrystallized HCl, * Corresponding author: Department of Biology, Islamic Azad [13]. (Me- University,Karaj branch Karaj, lran' Pyrrolg l- [ I -[4-methylphenylcvclohexvl] Ir a n .T e l: 0 2 6 1- 4 4 3 6 9 7 ' F a x: 026I - 8 P o . B o x : i I 4 8 5 - 313 ,Ka r a j, this compound was pre- PCP-Pyrrole) III' Finaily, s o la li@ kia ra c ir ' t 4418l56. E-nrail: