Download PDF
Arzneimittelforschung 2009; 59(4): 202-206
DOI: 10.1055/s-0031-1296386
Analgesics · Anti-inflammatories · Antiphlogistics · Antirheumatic Drugs
Editio Cantor Verlag Aulendorf (Germany)

Synthesis and Study on Analgesic Effects of l-[l-(4-Methylphenyl) (cyclohexyl)] 4-piperidinol and l-[l-(4-Methoxyphenyl) (cyclohexyl)] 4-piperidinol as Two New Phencyclidine Derivatives

Abbas Ahmadi
1   Department of Chemistry, Faculty of Science, Islamic Azad University Karaj Branch Karaj, (Iran)
,
Mohsen Khalili
2   Department of Physiology, Shahed University, Tehran, (Iran)
,
Sara Abbassi
1   Department of Chemistry, Faculty of Science, Islamic Azad University Karaj Branch Karaj, (Iran)
,
Mozhdeh Javadi
1   Department of Chemistry, Faculty of Science, Islamic Azad University Karaj Branch Karaj, (Iran)
,
Ali Mahmoudi
1   Department of Chemistry, Faculty of Science, Islamic Azad University Karaj Branch Karaj, (Iran)
,
Ramin Hajikhani
3   Department of Physiology, Faculty of Science Islamic Azad University, Karaj Branch, Karaj, (Iran)
› Author Affiliations
Further Information

Publication History

Publication Date:
13 December 2011 (online)

    Permissions and Reprints

Abstract

Phencyclidine (1-(1-phenylcyclohexyl) piperidine; CAS 956-90-1; PCP, I) has shown analgesic effects. Some of its derivatives have been synthesized and their biological properties have been studied. In this work, new methyl and methoxy hydroxyl derivatives of phencyclidine were synthesized and the analgesic effects of this compounds [(1-[1-(4-methylphe-nyl) (cyclohexyl)] 4-piperidinol, II), (1-[1-(4-methoxyphenyl) (cyclohexyl)] 4-piperidinol, III)] were studied using tail immersion test on rats and compared to PCP

The results showed that, II can produce more analgesic effects in the tail immersion test (as a model of acute thermal pain) in comparison to the PCP with a marked significant increase in tail immersion latency (15, 40 and 45 min after injection) but for III, only slight analgesic effects (15, 35 and 40 min after injection) was seen (without significant differences between pain thresholds)

Key words

Analgesics - CAS 956-90-1 - Phencyclidine, methoxy hydroxyl derivatives, methyl derivatives - Tail immersion test, acute thermal pain
 

  • References

  • 1 Greifenstein FE, Yoshitake J, De Vaulet M, Gajewski JE. A study of 1-arylcyclohexylamine for anesthesia. Anesth Analg. 1958; 37: 283-284
    PubMedGoogle Scholar
  • 2 Chen G, Ensor CR, Russell D, Bohner B. The pharmacology of l-(l-phenylcyclohexyl) piperidine-HCl. J Pharmacol Exp Ther. 1959; 127: 241-250
    PubMedGoogle Scholar
  • 3 Chen G, Weston JK. The analgesic and anesthetic effects of l-(l-phenylcyclohexyl) piperidine-HCl on the monkey. Anesth Analg. 1960; 39: 132-137
    PubMedGoogle Scholar
  • 4 Ahmadi A, Mahmoudi A. Synthesis with improved yield and study on analgesic effect of 2-methoxyphencyc\idine. Arzneimittelforschung. 2006; 56 (5) 346-350
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Al-Deeb OA. Synthesis and analgesic activity of new phen-cyclidine derivatives. Arzneimittelforschung. 1994; 44 (10) 1141-1144
    PubMedGoogle Scholar
  • 6 Honey CR, Mitjkovic Z, McDonald JF. Ketamine and phen-cyclidine cause a voltage-dependent block of responses to L-aspartic acid. Neurosci Lett. 1985; 61 (1–2) 135-139
    CrossrefPubMedGoogle Scholar
  • 7 Ahmadi A, Mahmoudi A. Synthesis and Biological Properties of 2-Hydroxy-l-(l-Phenyltetralin) Piperidine and some of its Intermediates as Derivatives of Phencyclidine. Arzneimittelforschung. 2005; 55 (9) 528-532
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Shimoyama N, Shimoyama M, Inturrisi CE. Ketamine attenuates reverses morphine tolerance in rodents. Anesthesiology. 1996; 85: 1357-1366
    CrossrefPubMedGoogle Scholar
  • 9 Fuman B, Aldinger G, Fauman M, Rosen P. Psychiatric sequelae of phencyclidine abuse. Clin Toxicol. 1976; 9: 529-538
    CrossrefPubMedGoogle Scholar
  • 10 Shebley M, Jushchyshyn MI, Hollenberg F. Selective pathways for the metabolism of phencyclidine by cytochrome P450 2B enzymes: identification of electrophilic methabo-lites, glutathione and N-acetyl cysteine adducts. Drug Me-tab Dispos. 2006; 34 (3) 375-383
    PubMedGoogle Scholar
  • 11 Kamenka JM, Hamon J, Vignon J, Phencyclidine derivatives. preparation method and pharmaceutical compositions containing same. United State Patent. 2002; 6: 342 511B1.
    PubMedGoogle Scholar
  • 12 Al-deeb OAA. New analgesic derived from the phencyclidine analogue thiencyclidine. Arzneimittelforschung. 1996; 46: 505-508
    PubMedGoogle Scholar
  • 13 Ogunbadeniyi AM, Adejare A. Syntheses of fluorinated phencyclidine analogs. J Fluor Chem. 2002; 114: 39-42
    CrossrefPubMedGoogle Scholar
  • 14 Ahmadi A, Shafiezadeh M, Fathollahi Y. Synthesis with improved yield and study on analgesic effect of 2-hydroxy-phencyclidine. Arzneimittelforschung. 2005; 55: 172-176
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Johnson PY, Pan R, Quan Wen J, Halfman CJ. Synthesis of amine derivatives of phencyclidine. J Org Chem. 1981; 46: 2049-2054
    CrossrefPubMedGoogle Scholar
  • 16 Kamenka JM, 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) 301-308
    PubMedGoogle Scholar
  • 17 Kamenka JM, Chiche B, Goudal R, Geneste P, Vignon J, Vincent JP et al Chemical synthesis and molecular pharmacology of hydroxylated l-(l-phenylcyclohexyl) piperidine derivatives. J Med Chem. 1982; 25: 431-435
    CrossrefPubMedGoogle Scholar
  • 18 Itzhak Y, Kalir A, Weissman BA, Cohen S. New analgesic drugs derived from phencyclidine. J Med Chem. 1981; 24: 496-499
    CrossrefPubMedGoogle Scholar
  • 19 Geneste P, Kamenka JM, Dessapt P. Method for Stereoselective Production of Substituted Cyclohexylcyanhydrines. Bull Soc Chim Fr. 1980; 11: 187-191
    PubMedGoogle Scholar
  • 20 Maddox VH, Godefroi EF, Parcell RF. The synthesis of phencyclidine and other 1-arylcyclohexylamines. J Med Chem. 1965; 8: 230-235
    CrossrefPubMedGoogle Scholar
  • 21 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
    CrossrefPubMedGoogle Scholar
  • 22 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) 286-292
    CrossrefPubMedGoogle Scholar
  • 23 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) 1669-1672
    PubMedGoogle Scholar
  • 24 Ibba M, Schiavi S, Abbiati G, Testa R. Effects of oral administration of nortriptyline, imipramine and Citalopram on morphine hot-plate and tail-immersion analgesia in rats. Boll Chim Farm. 1987; 126 (2) 75-80
    PubMedGoogle Scholar
  • 25 Sewell RD, Spencer PS. Antinociceptive activitiy of narcotic agonist and partial agonist analgesics and other agents in the tail-immersion test in mice and rats. Neuropharmacology. 1976; 15 (11) 683-688
    CrossrefPubMedGoogle Scholar
  • 26 Jones IA, Beaver RW, Schmoeger TL. J Org Chem. 1981; 46: 3330-3333
    CrossrefPubMed
  • 27 Ingold K. Structure and mechanism in organic chemistry. Cornell University Press; N. Y Ithaca: 1953
    Google Scholar
  • 28 Mori A, Noda Y, Mamiya T, Miyamoto Y, Nakajima A, Furu-kawa 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
    CrossrefPubMedGoogle Scholar
  • 29 Holtzman SG. Phencyclidine-like discriminative effects of opioids in the rat. J Pharmacol Exp Ther. 1980; 214: 614-619
    PubMedGoogle Scholar
  • 30 Balster RL, Woolverton WL. Continuous-access phencyclidine self-adminstration by rhesus monkeys leading to physical dependence. Psychopharmacology. 1980; 70: 5-10
    CrossrefPubMedGoogle Scholar