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Arzneimittelforschung 2011; 61(2): 92-97
DOI: 10.1055/s-0031-1296173
Analgesics · Anti-inflammatories · Antiphlogistics · Antirheumatic Drugs
Editio Cantor Verlag Aulendorf (Germany)

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

Abbas Ahmadi
1   Department of Chemistry, Faculty of Science, Islamic Azad University, Karaj branch, Karaj, Iran
,
Mohsen Khalili
2   Department of Physiology, Neuroscience and Herbal Medicine Research Centers, Shahed University, Tehran, Iran
,
Ramin Hajikhani
3   Department of Physiology, Faculty of Science, Islamic Azad University, Karaj branch, Karaj, Iran
,
Moslem Naserbakht
1   Department of Chemistry, Faculty of Science, Islamic Azad University, Karaj branch, Karaj, Iran
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Publikationsverlauf

Publikationsdatum:
28. November 2011 (online)

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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-mor-pholine, 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.

Key words

Acute and chronic pain - CAS 77-10-1 - CAS 2201-40-3 - Methyl morpholine derivative of phencyclidine - Tail immersion and formalin tests
 

  • References

  • 1 Ahmadi A, Mahmoudi A. Synthesis with improved yield and study on analgesic effect of 2-methoxyphencyclidine. Arzneimittelforschung. 2006; 56 () 346-50
    Thieme ConnectPubMedSuche in Google Scholar
  • 2 Al-deeb OAA. Synthesis and analgesic activity of new phencyclidine derivatives. Arzneimittelforschung. 1994; 44 (10) 1141-4
    PubMedSuche in Google Scholar
  • 3 Mori A, Noda Y, Mamiya T, Miyamoto Y, Nakajima A, Furukawa H et al Phencyclidine-induced discriminative stimulus is mediated via phencyclidine binding sites on the N-methyl-D-aspartate receptor-ion channel complex, not via sigma receptors. Behav Brain Res. 2001; 119: 33-40
    CrossrefPubMedSuche in Google Scholar
  • 4 Ahmadi A, Mahmoudi A. Synthesis and biological properties of 2-hydroxy-1-(1-phenyltetralin) piperidine and some of its intermediates as derivatives of phencyclidine. Arzneimittelforschung. 2005; 55 (9) 528-32
    Thieme ConnectPubMedSuche in Google Scholar
  • 5 Al-deeb OAA. New analgesics derived from the phencyclidine analogue thiencyclidine. Arzneimittelforschung. 1996; 46 (5) 505-8
    PubMedSuche in Google Scholar
  • 6 Ogunbadeniyi AM, Adejare A. Syntheses of fluorinated phencyclidine analogs. J Fluorine Chem. 2002; 114: 39-42
    CrossrefPubMedSuche in Google Scholar
  • 7 Ahmadi A, Shafiezadeh M, Fathollahi Y, Darvich MR, Mahmoudi A, Bahmani M et al Synthesis with improved yield and study on analgesic effect of 2-hydroxyphencyclidine. Arzneimittelforschung. 2005; 55 (3) 172-6
    Thieme ConnectPubMedSuche in Google Scholar
  • 8 Kamenka IM, Ung MSN, Herrmann P. Determination con-formationnelle de derives de la phencyclidine en vue d’une correlation acture-active. Eur J Med Chem Ther. 1979; 14 (IV) 301-8
    PubMedSuche in Google Scholar
  • 9 Kamenka IM, Chiche B, Goudal R, Geneste P, Vignon I, Vincent IP et al Chemical synthesis and molecular pharmacology of hydroxylated 1-(1-phenylcyclohexyl) piperidine derivatives. J Med Chem. 1982; 25: 431-5
    CrossrefPubMedSuche in Google Scholar
  • 10 Itzhak Y, Kalir A, Weissman BA, Cohen S. New analgesic drugs derived from phencyclidine. J Med Chem. 1981; 24: 496-9
    CrossrefPubMedSuche in Google Scholar
  • 11 Ahmadi A, Khalili M, Abbassi S, Javadi M, Mahmoudi A, Hajikhani R. Synthesis and Study on Analgesic Effects of 1-[1-[4-methylphenyl][cyclohexyl]-4-piperidinol and 1-[1-[4-methoxyphenyl][cyclohexyl]]-4-piperidinol as two new phencyclidine derivatives. Arzneimittelforschung. 2009; 59 (4) 202-6
    Thieme ConnectPubMedSuche in Google Scholar
  • 12 Ahmadi A, Khalili M, Mihandoust F, Barghi L. Synthesis and determination of acute and chronic pain activities of 1-[1-(3-methyphenyl)(tetralyl)]piperidine as a new derivative of phencyclidine via tail immersion and formalin tests. Arzneimittelforschung. 2010; 60 (1) 30-5
    Thieme ConnectPubMedSuche in Google Scholar
  • 13 Ahmadi A, Solati I, Hajikhani R, Onagh M, Javadi M. Synthesis and analgesic effects of 1-[1-(2-methylphenyl)(cyclo-hexyl)]-3-piperidinol as a new derivative of phencyclidine in mice. Arzneimittelforschung. 2010; 60 (8) 492-6
    Thieme ConnectPubMedSuche in Google Scholar
  • 14 Johnson PY, Pan R, Quan Wen I, Halfman CJ. Synthesis of amine derivatives of phencyclidine. J Org Chem. 191; 46: 2049-54
    PubMedSuche in Google Scholar
  • 15 Chen DM, Chen K, Wang H. Antithrombotic effects of morpholine and piperazine ring derivatives and their molecular mechanism. Yao Xue Xue Bao. 2003; 38 (9) 641-5
    PubMedSuche in Google Scholar
  • 16 Regnier G, Guillonneau C, Lepagnol I, Lestage P. Assignee: Adir et compagnie, Courbevoie, France; Morpholine compounds, compositions and use. United States Patent. 1991; 5026701
    PubMedSuche in Google Scholar
  • 17 Kaneyoshi K, Takayuki D, Mitsuo Y. Assignee: Takeda Chemical Industries LTD., Japan; Tetracyclic morpholine derivatives and their use as analgesics. European Patent. 1994; 0610793
    PubMedSuche in Google Scholar
  • 18 Rekka E, Retsas S, Demopoulos VJ, Kourounakis PN. Lipophilicity of some substituted morpholine derivatives synthesized as potential antinociceptive agents. Arch Pharm (Weinheim). 1990; 323 (1) 53-6
    CrossrefPubMedSuche in Google Scholar
  • 19 Soine WH. Clandestine drug synthesis. Med Res Rev. 1986; 6 (1) 41-74
    CrossrefPubMedSuche in Google Scholar
  • 20 Budd RD. Phencyclidine (PCP)-structure versus reactivity. Clin Toxicol. 1981; 18 (9) 1033-41
    CrossrefPubMedSuche in Google Scholar
  • 21 Geneste P, Kamenka JM, Dessapt P. Method for stereoselective production of substituted cyclohexylcyanhydrines. Bull Soc Chim Fr. 1980; II: 187-91
    PubMedSuche in Google Scholar
  • 22 Abdol-Rahman MO, Aboul-Eneim MN, Tammom GH. Action of Grignard reagents aryl lithium on 1,1-disubstituted cyclohexane derivatives. Egypt J Chem. 1975; 18 (3) 581-6
    PubMedSuche in Google Scholar
  • 23 Maddox VH, Godefroi EF, Parcell RF. The synthesis of phencyclidine and other 1-arylcyclohexylamines. J Med Chem. 1965; 8: 230-5
    CrossrefPubMedSuche in Google Scholar
  • 24 Ramabadran K, Bansinath M, Turndorf H, Puig MM. Tail immersion test for the evaluation of a nociceptive reaction in mice: methodological considerations. J Pharmacol Methods. 1989; 21 (1) 21-31
    CrossrefPubMedSuche in Google Scholar
  • 25 Molina N, Bedran-de-Castro MT, Bedran-de-Castro JC. Sex-related differences in the analgesic response to the rat tail immersion test. Braz J Med Biol Res. 1994; 27 (7) 1669-72
    PubMedSuche in Google Scholar
  • 26 Hamura H, Yoshida M, Shimizu K, Matsukura T, Suzuki H, Narita M et al Antinociceptive effect of the combination of pentazocine with morphine in the tail-immersion and scald-pain tests in rats. Jpn J Pharmacol. 2000; 83 (4) 286-92
    CrossrefPubMedSuche in Google Scholar
  • 27 Dubuisson D, Dennis SG. The formalin test: a quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain. 1977; 4 (2) 161-74
    CrossrefPubMedSuche in Google Scholar
  • 28 Mozayani A. Phencyclidine-effects on human performance and behavior. Forensic Sci Rev. 2003; 15 (1) 62-74
    PubMedSuche in Google Scholar
  • 29 Dougherty PM, Staats PS. Intrathecal drug therapy for chronic pain from basic science to clinical practice. Anesthesiology. 1999; 91: 189-918
    PubMedSuche in Google Scholar
  • 30 Proksch JW, Gentry WB, Owens SM. The effect of rate of drug administration on the extent and time course of phencyclidine distribution in rat brain, testis, and serum. Drug Metab Dispos. 2000; 28 (7) 742-7
    PubMedSuche in Google Scholar
  • 31 Deleuze-Masquefa C, Michaud M, Vignon J, Kamenka JM. 1-[1–2-Benzo[b]thiopheneyl)cyclohexyl]piperidine hydrochloride (BTCP) yields two active primary metabolites in vitro: synthesis, identification from rat liver microsome extracts, and affinity for the neuronal dopamine transporter. J Med Chem. 1997; 40 (25) 4019-25
    CrossrefPubMedSuche in Google Scholar