Naphthylpiperazine Explained

1-(1-Naphthyl)piperazine (1-NP) is a drug which is a phenylpiperazine derivative. It acts as a non-selective, mixed serotonergic agent, exerting partial agonism at the 5-HT_1A, 5-HT_1B, 5-HT_1D, 5-HT_1E, and 5-HT_1F receptors,^{[1] [2] [3]} while antagonizing the 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors.^{[4] [5] [6]} It has also been shown to possess high affinity for the 5-HT₃, 5-HT_5A, 5-HT₆, and 5-HT₇ receptors,^{[7] [8] [9] [10]} and may bind to 5-HT₄ and the SERT as well.^{[11] [12]} In animals it produces effects including hyperphagia,^{[13] [14] [15]} hyperactivity,^{[16] [17]} and anxiolysis,^{[18] [19] [20]} of which are all likely mediated predominantly or fully by blockade of the 5-HT_2C receptor.

See also

• Substituted piperazine
• Diphenylpiperazine
• Phenylpiperazine
• Quipazine

Notes and References

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2. Bai F, Yin T, Johnstone EM, etal . Molecular cloning and pharmacological characterization of the guinea pig 5-HT1E receptor . European Journal of Pharmacology . 484 . 2–3 . 127–39 . January 2004 . 14744596 . 10.1016/j.ejphar.2003.11.019.
3. Adham N, Kao HT, Schecter LE, etal . Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase . Proceedings of the National Academy of Sciences of the United States of America . 90 . 2 . 408–12 . January 1993 . 8380639 . 45671 . 10.1073/pnas.90.2.408. 1993PNAS...90..408A . free .
4. Conn PJ, Sanders-Bush E . Relative efficacies of piperazines at the phosphoinositide hydrolysis-linked serotonergic (5-HT-2 and 5-HT-1c) receptors . The Journal of Pharmacology and Experimental Therapeutics . 242 . 2 . 552–7 . August 1987 . 3039120 .
5. McKune CM, Watts SW . Characterization of the serotonin receptor mediating contraction in the mouse thoracic aorta and signal pathway coupling . The Journal of Pharmacology and Experimental Therapeutics . 297 . 1 . 88–95 . April 2001 . 11259531 .
6. Kursar JD, Nelson DL, Wainscott DB, Baez M . Molecular cloning, functional expression, and mRNA tissue distribution of the human 5-hydroxytryptamine2B receptor . Molecular Pharmacology . 46 . 2 . 227–34 . August 1994 . 8078486 .
7. Glennon RA, Ismaiel AE, McCarthy BG, Peroutka SJ . Binding of arylpiperazines to 5-HT3 serotonin receptors: results of a structure-affinity study . European Journal of Pharmacology . 168 . 3 . 387–92 . September 1989 . 2583244 . 10.1016/0014-2999(89)90802-9.
8. Wesołowska A . In the search for selective ligands of 5-HT5, 5-HT6 and 5-HT7 serotonin receptors . Polish Journal of Pharmacology . 54 . 4 . 327–41 . 2002 . 12523486 .
9. Lee M, Rangisetty JB, Pullagurla MR, etal . 1-(1-Naphthyl)piperazine as a novel template for 5-HT6 serotonin receptor ligands . Bioorganic & Medicinal Chemistry Letters . 15 . 6 . 1707–11 . March 2005 . 15745826 . 10.1016/j.bmcl.2005.01.031 .
10. Bard JA, Zgombick J, Adham N, Vaysse P, Branchek TA, Weinshank RL . Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase . The Journal of Biological Chemistry . 268 . 31 . 23422–6 . November 1993 . 10.1016/S0021-9258(19)49479-9 . 8226867 . free .
11. Curtet S, Soulier JL, Zahradnik I, etal . New arylpiperazine derivatives as antagonists of the human cloned 5-HT(4) receptor isoforms . Journal of Medicinal Chemistry . 43 . 20 . 3761–9 . October 2000 . 11020291. 10.1021/jm0009538.
12. Perrone R, Berardi F, Colabufo NA, etal . Design and synthesis of long-chain arylpiperazines with mixed affinity for serotonin transporter (SERT) and 5-HT(1A) receptor . The Journal of Pharmacy and Pharmacology . 57 . 10 . 1319–27 . October 2005 . 16259761 . 10.1211/jpp.57.10.0011 . 84457274 .
13. Kennett GA, Curzon G . Evidence that hypophagia induced by mCPP and TFMPP requires 5-HT1C and 5-HT1B receptors; hypophagia induced by RU 24969 only requires 5-HT1B receptors . Psychopharmacology . 96 . 1 . 93–100 . 1988 . 2906446 . 10.1007/BF02431539. 21417374 .
14. Gibson EL, Kennedy AJ, Curzon G . d-Fenfluramine- and d-norfenfluramine-induced hypophagia: differential mechanisms and involvement of postsynaptic 5-HT receptors . European Journal of Pharmacology . 242 . 1 . 83–90 . September 1993 . 8223940 . 10.1016/0014-2999(93)90013-8.
15. Schechter LE, Simansky KJ . 1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI) exerts an anorexic action that is blocked by 5-HT2 antagonists in rats . Psychopharmacology . 94 . 3 . 342–6 . 1988 . 3128809 . 10.1007/bf00174687. 6463496 .
16. Perveen T, Rafiq R, Haider S, Haleem DJ . Increased serotonergic functions following administration of 1-(1-naphthyl) piperazine in propranolol injected rats . . 19 . 3 . 194 . July 2006 . 16935825 .
17. Kennett GA . 5-HT1C receptor antagonists have anxiolytic-like actions in the rat social interaction model . Psychopharmacology . 107 . 2–3 . 379–84 . 1992 . 1352056 . 10.1007/BF02245165. 44041403 .
18. Pruus K, Rudisaar R, Vaarmann A, Matto V, Allikmets L . 1-(1-naphthyl)-piperazine, a mixed 5-HT1A and 5-HT2A/2C receptor ligand, elicits an anxiolytic-like effect in the open-field test without changes in 5-HT metabolism . Methods and Findings in Experimental and Clinical Pharmacology . 24 . 3 . 151–7 . April 2002 . 12087877 . 10.1358/mf.2002.24.3.802300.
19. Gibson EL, Barnfield AM, Curzon G . Evidence that mCPP-induced anxiety in the plus-maze is mediated by postsynaptic 5-HT2C receptors but not by sympathomimetic effects . Neuropharmacology . 33 . 3–4 . 457–65 . 1994 . 7984284 . 10.1016/0028-3908(94)90076-0. 3029085 .
20. Kennett GA, Pittaway K, Blackburn TP . Evidence that 5-HT2c receptor antagonists are anxiolytic in the rat Geller-Seifter model of anxiety . Psychopharmacology . 114 . 1 . 90–6 . February 1994 . 7846211 . 10.1007/BF02245448. 12720128 .