Login Register Cart 0
Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Synthesis and Antinociceptive Activity of Newly Modified Amine Analogs of Phencyclidine in Mice

Author(s): Maryam Shokrollahi, Marjaneh Samadizadeh, Mohsen Khalili, Seyed Ali Sobhanian* and Abbas Ahmadi

Volume 25, Issue 11, 2022

Published on: 05 January, 2022

Page: [1966 - 1972] Pages: 7

DOI: 10.2174/1386207325666211005155128

Price: $65

Abstract

Background: Phencyclidine (PCP, I) and its substituted analogs are significant and broadly abused psychotomimetic drugs that affect the central nervous system. They possess many pharmacological properties due to the presence of specific receptors in the brain.

Aims and Objective: Methyl group, despite strong electron-donating and characters of dipole moments, was placed on various positions of phenyl and amine moieties of phencyclidine along with the substitution of benzylamine, piperazine, and aniline derivatives in place of piperidine ring of phencyclidine to create novel compounds of the core with analgesic properties.

Materials and Methods: For evaluation of the analgesic activities of newly synthesized compounds, they were screened by tests of tail immersion (thermal) and formalin (chemical) pains. The obtained data with the control and PCP groups were also compared.

Results: The outcomes indicated that some new compounds have more antinociceptive effects than PCP in tail immersion and formalin tests. In the tail immersion test, the methyl piperazine analog (III) shows more efficacy than others. In the formalin test, none of the compounds are as effective as phencyclidine at the earliest time-point, but compounds IV and V show effectiveness during the second stage of formalin pain.

Conclusion: It can be concluded that the methyl-piperazine analog of phencyclidine was the best candidate to decrease acute thermal pain, and benzylamine derivatives were suitable candidates to reduce chemical pains.

Keywords: Synthesis, antinociceptive activity, benzylamine, piperazine, aniline, phencyclidine’s derivatives, central nervous, tail immersion, formalin tests.

« Previous Next »
Graphical Abstract

[1]
Carlson, K.M.; Wagner, G.C. Effects of phencyclidine on schedule-controlled responding following neurotoxic lesions of the striatum. Life Sci., 2005, 77(4), 372-385.
[http://dx.doi.org/10.1016/j.lfs.2004.08.043] [PMID: 15894007]
[2]
Shokrollahi, M.; Samadizadeh, M.; Khalili, M.; Sobhanian, S.A.; Ahmadi, A. New Amine and aromatic substituted analogues of phency-clidine: synthesis and determination of acute and chronic pain activities. Comb. Chem. High Throughput Screen., 2019, 22(8), 570-576.
[http://dx.doi.org/10.2174/1386207322666191016152157] [PMID: 31622215]
[3]
Ferle-Vidović, A.; Kaštelan, M.; Petrović, D.; Šuman, L.; Kaselj, M.; Škare, D.; Mlinarić-Majerski, K. Synthesis and biological activity of phencyclidine and its adamantylamine derivatives. Eur. J. Med. Chem., 1993, 28(3), 243-250.
[http://dx.doi.org/10.1016/0223-5234(93)90140-A]
[4]
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), 202-206.
[PMID: 19517897]
[5]
Ahmadi, A.; Khalili, M.; Hajikhani, R.; Naserbakht, M. New morpholine analogues of phencyclidine: Chemical synthesis and pain percep-tion in rats. Pharmacol. Biochem. Behav., 2011, 98(2), 227-233.
[http://dx.doi.org/10.1016/j.pbb.2010.12.019] [PMID: 21215770]
[6]
Ahmadi, A.; Kermani, M.; Naderi, N.; Hajikhani, R.; Rezaee, N.M.; Javadi, M.; Niknafs, B.N. Synthesis and antinociceptive behaviors of new methyl and hydroxyl derivatives of phencyclidine. Curr. Med. Chem., 2012, 19(5), 763-769.
[http://dx.doi.org/10.2174/092986712798992057] [PMID: 22214446]
[7]
Ahmadi, A.; Khalili, M.; Marami, S.; Ghadiri, A.; Nahri-Niknafs, B. Synthesis and pain perception of new analogues of phencyclidine in NMRI male mice. Mini Rev. Med. Chem., 2014, 14(1), 64-71.
[http://dx.doi.org/10.2174/1389557513666131119203551] [PMID: 24251803]
[8]
Ahmadi, A.; Khalili, M.; Fallah, M.; Nahri-Niknafs, B. Synthesis and analgesic properties of new modified analogs of phencyclidine with specific binding on PCP receptor or dopamine inhibition reuptake activities. Pharm. Chem. J., 2015, 49(9), 613-619.
[http://dx.doi.org/10.1007/s11094-015-1339-0]
[9]
Ahmadi, A.; Khalili, M.; Barzin, M.; Pooladi, M.; Bakhtiari, F.; Barjeste, M.; Nahri-Niknafs, B. Synthesis and antinociception properties of phencyclidinederivatives with modified aromatic or cycloalkyl rings and aminogroup. Monatsh. Chem., 2016, 147(2), 457-464.
[http://dx.doi.org/10.1007/s00706-015-1472-1]
[10]
Ahmadi, A.; Khalili, M.; Mirza, B.; Mohammadi-Diz, M.; Azami-Lorestani, F.; Ghaderi, P.; Nahri-Niknafs, B. Synthesis and Antinocicep-tion Activities of Some Novel Derivatives of Phencyclidine with Substituted Aminobenzothiazoles. Mini Rev. Med. Chem., 2017, 17(1), 78-84.
[http://dx.doi.org/10.2174/1389557516666160428112532] [PMID: 27121715]
[11]
Okunrobo, L.O.; Usifoh, C.O. Ring opening of phthalimide derivatives with benzylamine: Formation of carboxamides and their pharmaco-logical evaluation. Indian J. Pharm. Sci., 2007, 69(1), 96-100.
[http://dx.doi.org/10.4103/0250-474X.32116]
[12]
Lommen, G.; De Bruyn, M.; Schroven, M.; Verschueren, W.; Janssens, W.; Verrelst, J.; Leysen, J. The discovery of a series of new non-indole 5HT1D agonists. Bioorg. Med. Chem. Lett., 1995, 5(22), 2649-2654.
[http://dx.doi.org/10.1016/0960-894X(95)00473-7]
[13]
Choi, D.; Stables, J.P.; Kohn, H. Synthesis and anticonvulsant activities of N-Benzyl-2-acetamidopropionamide derivatives. J. Med. Chem., 1996, 39(9), 1907-1916.
[http://dx.doi.org/10.1021/jm9508705] [PMID: 8627614]
[14]
Mason, P.A.; Sturman, G. Some pharmacological properties of piperazine. Br. J. Pharmacol., 1972, 44(2), 169-176.
[http://dx.doi.org/10.1111/j.1476-5381.1972.tb07252.x] [PMID: 4668588]
[15]
Natsuka, K.; Nakamura, H.; Uno, H.; Umemoto, S. Studies on 1-substituted 4-(1,2-diphenylethyl)piperazine derivatives and their analge-sic activities. 1. J. Med. Chem., 1975, 18(12), 1240-1244.
[http://dx.doi.org/10.1021/jm00246a014] [PMID: 1195277]
[16]
Pudukulatham, Z.; Zhang, F.X.; Gadotti, V.M.; M’Dahoma, S.; Swami, P.; Tamboli, Y.; Zamponi, G.W. Synthesis and characterization of a disubstituted piperazine derivative with T-type channel blocking action and analgesic properties. Mol. Pain, 2016, 12, 1744806916641678.
[http://dx.doi.org/10.1177/1744806916641678] [PMID: 27053601]
[17]
Sicardi, S.M.; Martiarena, J.L.; Iglesias, M.T. Mutagenic and analgesic activities of aniline derivatives. J. Pharm. Sci., 1991, 80(8), 761-764.
[http://dx.doi.org/10.1002/jps.2600800811] [PMID: 1791537]
[18]
Ahmadi, A.; Khalili, M.; Ahmadian, S.; Shahghobadi, N.; Nahri-Niknafs, B. synthesis and pharmacological evaluation of new chemical entities based on paracetamol and their ibuprofen conjugates as novel and superior analgesic and anti-inflammatory candidates. Pharm. Chem. J., 2014, 48, 109-115.
[http://dx.doi.org/10.1007/s11094-014-1059-x]
[19]
Dubuisson, D.; Dennis, S.G. 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), 161-174.
[http://dx.doi.org/10.1016/0304-3959(77)90130-0] [PMID: 564014]
[20]
Ramabadran, K.; Bansinath, M.; Turndorf, H.; Puig, M.M. Tail immersion test for the evaluation of a nociceptive reaction in mice. Meth-odological considerations. J. Pharmacol. Methods, 1989, 21(1), 21-31.
[http://dx.doi.org/10.1016/0160-5402(89)90019-3] [PMID: 2704245]
[21]
Maddox, V.H.; Godefroi, E.F.; Parcell, R.F. The synthesis of phencyclidine and other larylcyclohexylamines. J. Med. Chem., 1965, 8, 230-235.
[http://dx.doi.org/10.1021/jm00326a019] [PMID: 14332667]
[22]
Dworkin, R.H.; Backonja, M.; Rowbotham, M.C.; Allen, R.R.; Argoff, C.R.; Bennett, G.J.; Bushnell, M.C.; Farrar, J.T.; Galer, B.S.; Hay-thornthwaite, J.A.; Hewitt, D.J.; Loeser, J.D.; Max, M.B.; Saltarelli, M.; Schmader, K.E.; Stein, C.; Thompson, D.; Turk, D.C.; Wallace, M.S.; Watkins, L.R.; Weinstein, S.M. Advances in neuropathic pain: Diagnosis, mechanisms, and treatment recommendations. Arch. Neurol., 2003, 60(11), 1524-1534.
[http://dx.doi.org/10.1001/archneur.60.11.1524] [PMID: 14623723]
[23]
Johnson, K.M.; Jones, S.M. Neuropharmacology of phencyclidine: Basic mechanisms and therapeutic potential. Annu. Rev. Pharmacol. Toxicol., 1990, 30, 707-750.
[http://dx.doi.org/10.1146/annurev.pa.30.040190.003423] [PMID: 2160793]

Rights & Permissions Print Cite
Article Metrics
25
2
© 2024 Bentham Science Publishers | Privacy Policy