Selexipag: A selective prostacyclin receptor agonist that does not affect rat gastric function

Journal of Pharmacology and Experimental Therapeutics

Volumn 335, Issue 1, 2010, Pages 249-255

  Morrison, Keith ^a   Ernst, Roland ^a   Hess, Patrick ^a   Studer, Rolf ^a   Clozel, Martine ^a  

^a ACTELION PHARMACEUTICALS LTD   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ACT 333679; BERAPROST; DRUG METABOLITE; ILOPROST; PROSTACYCLIN RECEPTOR; PROSTACYCLIN RECEPTOR AGONIST; PROSTAGLANDIN E RECEPTOR; PROSTAGLANDIN RECEPTOR STIMULATING AGENT; PYRAZINE DERIVATIVE; SELEXIPAG; THROMBOXANE RECEPTOR; UNCLASSIFIED DRUG; UNIPROST; [4 [(5,6 DIPHENYLPYRAZIN 2)(ISOPROPYL)AMINO]BUTOXY]ACETIC ACID; ACETAMIDE DERIVATIVE; MESSENGER RNA; PROSTACYCLIN; PROSTAGLANDIN E2; SULPROSTONE; TREPROSTINIL;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFECT; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; INTESTINE ABSORPTION; MALE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; STOMACH EMPTYING; STOMACH FUNCTION; STOMACH FUNDUS; STOMACH MUSCLE; AGONISTS; ANALOGS AND DERIVATIVES; ANIMAL; BIOSYNTHESIS; DOSE RESPONSE; DRUG EFFECTS; GASTROINTESTINAL TRANSIT; GENETICS; HUMAN; MUSCLE CONTRACTION; PHYSIOLOGY; PULMONARY ARTERY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; STOMACH;

ACETAMIDES; ANIMALS; DINOPROSTONE; DOSE-RESPONSE RELATIONSHIP, DRUG; EPOPROSTENOL; GASTRIC EMPTYING; GASTROINTESTINAL TRANSIT; HUMANS; ILOPROST; MALE; MUSCLE CONTRACTION; PULMONARY ARTERY; PYRAZINES; RATS; RECEPTORS, EPOPROSTENOL; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, MESSENGER; STOMACH;

EID: 77957237185     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.110.169748     Document Type: Article

References (33)

1. Abramovitz M, Adam M, Boie Y, Carrière MC, Denis D, Godbout C, Lamontagne S, Rochette C, Sawyer N, Tremblay NM, et al. (2000) The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs. Biochim Biophys Acta 1483:285-293.
2. Andrews PL and Horn CC (2006) Signals for nausea and emesis: implications for models of upper gastrointestinal diseases. Auton Neurosci 125:100-115.
3. Behm DJ, Ogbonna A, Wu C, Burns-Kurtis CL, and Douglas SA (2009) Epoxyeicosatrienoic acids function as selective, endogenous antagonists of native thromboxane receptors: identification of a novel mechanism of vasodilation. J Pharmacol Exp Ther 328:231-239.
4. Bennett A, Jarosik C, Sanger GJ, and Wilson DE (1980) Antagonism of prostanoid-induced contractions of rat gastric fundus muscle by SC-19220, sodium meclofenamate, indomethacin or trimethoquinol. Br J Pharmacol 71:169-175. (Pubitemid 11167776)
5. Bradner WT and Schurig JE (1981) Toxicology screening in small animals. Cancer Treat Rev 8:93-102.
6. Dey I, Lejeune M, and Chadee K (2006) Prostaglandin E2 receptor distribution and function in the gastrointestinal tract. Br J Pharmacol 149:611-623. (Pubitemid 44748054)
7. Dong YJ, Jones RL, and Wilson NH (1986) Prostaglandin E receptor subtypes in smooth muscle: agonist activities of stable prostacyclin analogues. Br J Pharmacol 87:97-107.
8. Forrest AS, Hennig GW, Jokela-Willis S, Park CD, and Sanders KM (2009) Prostaglandin regulation of gastric slow waves and peristalsis. Am J Physiol Gastrointest Liver Physiol 296:G1180-G1190.
9. Fukuhara A, Imai T, and Otagiri M (1996) Stereoselective disposition of flurbiprofen from a mutual prodrug with a histamine H2-antagonist to reduce gastrointestinal lesions in the rat. Chirality 8:494-502.
10. Gallant M, Carrière MC, Chateauneuf A, Denis D, Gareau Y, Godbout C, Greig G, Juteau H, Lachance N, Lacombe P, et al. (2002) Structure-activity relationship of biaryl acylsulfonamide analogues on the human EP3 prostanoid receptor. Bioorg Med Chem Lett 12:2583-2586.
11. Giles H, Leff P, Bolofo ML, Kelly MG, and Robertson AD (1989) The classification of prostaglandin DP receptors in platelets and vasculature using BW A868C, a novel, selective and potent competitive antagonist. Br J Pharmacol 96:291-300.
12. Gomberg-Maitland M and Olschewski H (2008) Prostacyclin therapies for the treatment of pulmonary arterial hypertension. Eur Respir J 31:891-901.
13. Holmes AM, Rudd JA, Tattersall FD, Aziz Q, and Andrews PL (2009) Opportunities for the replacement of animals in the study of nausea and vomiting. Br J Pharmacol 157:865-880.
14. Humbert M, Sanchez O, Fartoukh M, Jagot JL, Le Gall C, Sitbon O, Parent F, and Simonneau G (1999) Short-term and long-term epoprostenol (prostacyclin) therapy in pulmonary hypertension secondary to connective tissue diseases: results of a pilot study. Eur Respir J 13:1351-1356.
15. Jones RL, Wise H, Clark R, Whiting RL, and Bley KR (2006) Investigation of the prostacyclin (IP) receptor antagonist RO1138452 on isolated blood vessel and platelet preparations. Br J Pharmacol 149:110-120.
16. Kan KK, Jones RL, Ngan MP, and Rudd JA (2002) Actions of prostanoids to induce emesis and defecation in the ferret. Eur J Pharmacol 453:299-308.
17. Kiriyama M, Ushikubi F, Kobayashi T, Hirata M, Sugimoto Y, and Narumiya S (1997) Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells. Br J Pharmacol 122:217-224.
18. Kuwano K, Hashino A, Asaki T, Hamamoto T, Yamada T, Okubo K, and Kuwabara K (2007) 2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N- (methylsulfonyl) acetamide (NS-304), an orally available and long-acting prostacyclin receptor agonist prodrug. J Pharmacol Exp Ther 322:1181-1188.
19. Kuwano K, Hashino A, Noda K, Kosugi K, and Kuwabara K (2008) A long-acting and highly selective prostacyclin receptor agonist prodrug, 2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl) acetamide (NS-304), ameliorates rat pulmonary hypertension with unique relaxant responses of its active form, {4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino] butoxy}acetic acid (MRE-269), on rat pulmonary artery. J Pharmacol Exp Ther 326:691-699.
20. Lawrence RA, Jones RL, and Wilson NH (1992) Characterization of receptors involved in the direct and indirect actions of prostaglandins E and I on the guineapig ileum. Br J Pharmacol 105:271-278.
21. Lumley P, White BP, and Humphrey PP (1989) GR32191, a highly potent and specific thromboxane A2 receptor blocking drug on platelets and vascular and airways smooth muscle in vitro. Br J Pharmacol 97:783-794.
22. McCormick C, Jones RL, Kennedy S, and Wadsworth RM (2010) Activation of prostanoid EP receptors by prostacyclin analogues in rabbit iliac artery: implications for anti-restenotic potential. Eur J Pharmacol 641:160-167.
23. Meanwell NA, Rosenfeld MJ, Trehan AK, Wright JJ, Brassard CL, Buchanan JO, Federici ME, Fleming JS, Gamberdella M, Hartl KS, et al. (1994) Non-prostanoid prostacyclin mimetics. 6. Derivatives of 2-[3-[2-(4,5-diphenyl-2- oxazolyl)ethyl]phenoxy] acetic acid modified β-to the oxazole ring. Drug Des Discov 11:73-89.
24. Narumiya S, Sugimoto Y, and Ushikubi F (1999) Prostanoid receptors: structures, properties, and functions. Physiol Rev 79:1193-1226.
25. Okada Y, Hara A, Ma H, Xiao CY, Takahata O, Kohgo Y, Narumiya S, and Ushikubi F (2000) Characterization of prostanoid receptors mediating contraction of the gastric fundus and ileum: studies using mice deficient in prostanoid receptors. Br J Pharmacol 131:745-755.
26. Pal A, Brasseur JG, and Abrahamsson B (2007) A stomach road or "Magenstrasse" for gastric emptying. J Biomech 40:1202-1210.
27. Qian YM and Jones RL (1995) Inhibition of rat colon contractility by prostacyclin (IP-) receptor agonists: involvement of NANC neurotransmission. Br J Pharmacol 115:163-171.
28. Sitbon O, Humbert M, Nunes H, Parent F, Garcia G, Hervé P, Rainisio M, and Simonneau G (2002) Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival. J Am Coll Cardiol 40:780-788.
29. Tuder RM, Cool CD, Geraci MW, Wang J, Abman SH, Wright L, Badesch D, and Voelkel NF (1999) Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am J Respir Crit Care Med 159:1925-1932.
30. van Rossum JM (1963) Cumulative dose-response curves. II. Technique for the making of dose-response curves in isolated organs and the evaluation of drug parameters. Arch Int Pharmacodyn Ther 143:299-330.
31. Vane JR (1957) A sensitive method for the assay of 5-hydroxytryptamine. Br J Pharmacol 12:344-349.
32. Wallace JL (2008) Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn't the stomach digest itself? Physiol Rev 88:1547-1565.
33. Widlitz AC, McDevitt S, Ward GR, and Krichman A (2007) Practical aspects of continuous intravenous treprostinil therapy. Crit Care Nurse 27:41-50.