Characterization of vabicaserin (SCA-136), a selective 5-hydroxytryptamine 2C receptor agonist

Journal of Pharmacology and Experimental Therapeutics

Volumn 337, Issue 3, 2011, Pages 673-680

  Dunlop, John ^a   Watts, Stephanie W ^b   Barrett, James E ^a   Coupet, Joseph ^a   Harrison, Boyd ^a   Mazandarani, Hossein ^a   Nawoschik, Stanley ^a   Pangalos, Menelas N ^a   Ramamoorthy, Siva ^a   Schechter, Lee ^a   Smith, Deborah ^a   Stack, Gary ^a   Zhang, Jean ^a   Zhang, Guoming ^a   Rosenzweig Lipson, Sharon ^a  

^a PFIZER INC   (United States)

^b MICHIGAN STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2,5 DIMETHOXY 4 METHYLAMPHETAMINE; ALPHA ADRENERGIC RECEPTOR; CALCIUM; DEOXYCORTICOSTERONE ACETATE; DOPAMINE RECEPTOR; IODINE 125; SEROTONIN 2B RECEPTOR; SEROTONIN 2C RECEPTOR; VABICASERIN;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; CALCIUM MOBILIZATION; CHO CELL; COLON; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; FEMALE; GENETIC TRANSFECTION; HUMAN; HUMAN TISSUE; IN VITRO STUDY; INTESTINE CONTRACTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; RECEPTOR UPREGULATION; STOMACH FUNDUS;

ANIMALS; ANTIPSYCHOTIC AGENTS; BINDING SITES; CELL LINE; CHO CELLS; CRICETINAE; CRICETULUS; HETEROCYCLIC COMPOUNDS WITH 4 OR MORE RINGS; HUMANS; MALE; MOLECULAR TARGETED THERAPY; MUSCLE CONTRACTION; MUSCLE, SMOOTH; PROTEIN BINDING; RATS; RATS, SPRAGUE-DAWLEY; RECEPTOR, SEROTONIN, 5-HT2A; RECEPTOR, SEROTONIN, 5-HT2B; RECEPTOR, SEROTONIN, 5-HT2C; RECOMBINANT PROTEINS; SEROTONIN; SEROTONIN 5-HT2 RECEPTOR AGONISTS; SEROTONIN 5-HT2 RECEPTOR ANTAGONISTS; SIGNAL TRANSDUCTION;

EID: 79956204058     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.111.179572     Document Type: Article

References (21)

1. Barnes NM and Sharp T (1999) A review of central 5-HT receptors and their function. Neuropharmacology 38:1083-1152. (Pubitemid 29292403)
2. Baxter G, Kennett G, Blaney F, and Blackburn T (1995) 5-HT2 receptor subtypes: a family re-united? Trends Pharmacol Sci 16:105-110.
3. Baxter GS, Murphy OE, and Blackburn TP (1994) Further characterization of 5-hydroxytryptamine receptors (putative 5-HT2B) in rat stomach fundus longitudinal muscle. Br J Pharmacol 112:323-331. (Pubitemid 24151747)
4. Berg KA, Maayani S, Goldfarb J, and Clarke WP (1998) Pleiotropic behavior of 5-HT2A and 5-HT2C receptor agonists. Ann NY Acad Sci 861:104-110. (Pubitemid 29047706)
5. Borman RA, Tilford NS, Harmer DW, Day N, Ellis ES, Sheldrick RL, Carey J, Coleman RA, and Baxter GS (2002) 5-HT(2B) receptors play a key role in mediating the excitatory effects of 5-HT in human colon in vitro. Br J Pharmacol 135:1144-1151. (Pubitemid 34259114)
6. Cheng Y and Prusoff WH (1973) Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol 22:3099-3108.
7. Dunlop J, Sabb AL, Mazandarani H, Zhang J, Kalgaonker S, Shukhina E, Sukoff S, Vogel RL, Stack G, Schechter L, et al. (2005) WAY-163909 [(7bR, 10aR)-1,2,3,4,8,9,10, 10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7,1 hi]indole], a novel 5-hydroxytryptamine 2C receptor-selective agonist with anorectic activity. J Pharmacol Exp Ther 313:862-869.
8. Fitzgerald LW, Burn TC, Brown BS, Patterson JP, Corjay MH, Valentine PA, Sun JH, Link JR, Abbaszade I, Hollis JM, et al. (2000) Possible role of valvular serotonin 5-HT(2B) receptors in the cardiopathy associated with fenfluramine. Mol Pharmacol 57:75-81. (Pubitemid 30033262)
9. Launay JM, Hervé P, Peoc'h K, Tournois C, Callebert J, Nebigil CG, Etienne N, Drouet L, Humbert M, Simonneau G, et al. (2002) Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension. Nat Med 8:1129-1135.
10. Marquis KL, Sabb AL, Logue SF, Brennan JA, Piesla MJ, Comery TA, Grauer SM, Ashby CR Jr, Nguyen HQ, Dawson LA, et al. (2007) WAY-163909 [(7bR,10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7, 1hi]indole]: a novel 5-hydroxytryptamine 2C receptor-selective agonist with preclinical antipsychotic-like activity. J Pharmacol Exp Ther 320:486-496.
11. 2c receptor agonists: potential for the treatment of obesity. Mol Interv 5:282-291.
12. Ramamoorthy P, Beyer C, Brennan J, Dunlop J, Gove S, Grauer S, Harrison BL, Lin Q, Malberg J, Marquis K, et al. (2006) Discovery of SCA-136, a novel 5-HT2C agonist, for the treatment of schizophrenia, at the 231st American Chemical Society National Meeting; 2006 March 26-30; Atlanta, GA. American Chemical Society, Washington, DC.
13. Rosenzweig-Lipson S, Sabb A, Stack G, Mitchell P, Lucki I, Malberg JE, Grauer S, Brennan J, Cryan JF, Sukoff Rizzo SJ, et al. (2007) Antidepressant-like effects of the novel, selective, 5-HT2C receptor agonist WAY-163909 in rodents. Psychopharmacology 192:159-170. (Pubitemid 46669211)
14. Rothman RB, Baumann MH, Savage JE, Rauser L, McBride A, Hufeisen SJ, and Roth BL (2000) Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications. Circulation 102:2836-2841.
15. Siuciak JA, Chapin DS, McCarthy SA, Guanowsky V, Brown J, Chiang P, Marala R, Patterson T, Seymour PA, Swick A, et al. (2007) CP-809,101, a selective 5-HT2C agonist, shows activity in animal models of antipsychotic activity. Neuropharmacology 52:279-290. (Pubitemid 46123348)
16. Smith SR, Prosser WA, Donahue DJ, Morgan ME, Anderson CM, Shanahan WR, and APD356-004 Study Group (2009) Lorcaserin (APD356), a selective 5-HT(2C) agonist, reduces body weight in obese men and women. Obesity 17:494-503.
17. Thomsen WJ, Grottick AJ, Menzaghi F, Reyes-Saldana H, Espitia S, Yuskin D, Whelan K, Martin M, Morgan M, Chen W, et al. (2008) Lorcaserin, a novel selective human 5-hydroxytryptamine2C agonist: in vitro and in vivo pharmacological characterization. J Pharmacol Exp Ther 325:577-587. (Pubitemid 351574813)
18. Wacker DA and Miller KJ (2008) Agonists of the serotonin 5-HT2C receptor: preclinical and clinical progression in multiple diseases. Curr Opin Drug Discov Devel 11:438-445. (Pubitemid 351950839)
19. Watts SW, Baez M, and Webb RC (1996) The 5-hydroxytryptamine2B receptor and 5-HT receptor signal transduction in mesenteric arteries from deoxycorticosterone acetate-salt hypertensive rats. J Pharmacol Exp Ther 277:1103-1113.
20. Watts SW and Fink GD (1999) 5-HT2B-receptor antagonist LY-272015 is antihypertensive in DOCA-salt-hypertensive rats. Am J Physiol Heart Circ Physiol 276:H944-H952. (Pubitemid 29157467)
21. Werry TD, Stewart GD, Crouch MF, Watts A, Sexton PM, and Christopoulos A (2008) Pharmacology of 5HT2C receptor-mediated ERK1/2 phosphorylation: agonist-specific activation pathways and the impact of RNA editing. Biochem Pharmacol 76:1276-1287.