PRX-00023, a selective 5-HT1A receptor agonist for depression

Current Opinion in Investigational Drugs

Volumn 8, Issue 1, 2007, Pages 78-86

  De Paulis, Tomas ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

AMPHETAMINE; BUSPIRONE; CHLORDIAZEPOXIDE; N [3 [4 [4 (CYCLOHEXYLMETHYLSULFONAMIDO)BUTYL] 1 PIPERAZINYL]PHENYL]ACETAMIDE; PLACEBO; N (3 (4 (4 CYCLOHEXYLMETHANESULFONYLAMINOBUTYL)PIPERAZIN 1 YL)PHENYL)ACETAMIDE; N-(3-(4-(4-CYCLOHEXYLMETHANESULFONYLAMINOBUTYL)PIPERAZIN-1-YL)PHENYL)ACETAMIDE; PIPERAZINE DERIVATIVE; SEROTONIN 1A RECEPTOR; SULFONAMIDE; UNCLASSIFIED DRUG;

ANXIETY DISORDER; CLINICAL TRIAL; DEPRESSION; DIZZINESS; DRUG METABOLISM; DRUG SCREENING; DRUG SYNTHESIS; GENERALIZED ANXIETY DISORDER; HEADACHE; HUMAN; HYPERTHERMIA; NONHUMAN; REVIEW; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION; ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; DRUG POTENTIATION; MAJOR DEPRESSION; SMOKING CESSATION;

ANIMALS; CLINICAL TRIALS; DEPRESSIVE DISORDER, MAJOR; HUMANS; MOLECULAR STRUCTURE; PIPERAZINES; RECEPTOR, SEROTONIN, 5-HT1A; SMOKING CESSATION; SULFONAMIDES;

EID: 33947395654     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (57)

1. 2-adrenoceptor antagonist activity of ipsapirone and gepirone is mediated by their common metabolite 1-(2-pyrimidinyl)piperazine (PmP). Biachi G, Caccia S, Della Vedova F, Garattini S EUR J PHARMACOL 1988 151 3 365-371
2. Metabolism and disposition of buspirone. Gammans RE, Mayol RF, LaBudde JA AM J MED 1986 80 41-51
3. Buspirone analogues. 2. Structure-activity relationships of aromatic imide derivatives. New JS, Yevich JP, Eison MS, Taylor DP, Eison AS, Riblet LA, VanderMaelen CP, Temple DL J MED CHEM 1986 29 8 1476-1482
4. Complex effects of age and gender on hypothermic, adrenocorticotrophic hormone and cortisol responses to ipsapirone challenge in normal subjects. Gelfin Y, Lerer B, Lesch KP, Gorfine M, Allolio B PSYCHOPHARMACOL 1995 120 3 356-364
5. Disposition of the psychotropic drugs buspirone, MJ-13805 and peribidil, and their common active metabolite 1-(2-pyrimidinyl)piperazine in the rat. Caccia S, Fong MH, Guiso G XENOBIOT 1985 15 10 835-844
6. 1A receptor agonists: Recent developments and controversial issues. De Vry J PSYCHOPHARMACOL 1995 121 1 1-26
7. Bayer Hoare Govett ANALYST REPORT 1997
8. Disposition kinetics of buspirone in patients with renal or hepatic impairment after administration of single and multiple doses. Barbhaya RH, Shukla UA, Pfeffer M, Pittman KA, Shrotriya R, Laroudie C, Gammans RE EUR J CLIN PHARMACOL 1994 46 1 41-47
9. QT interval prolongation and cardiac risk assessment for novel drugs. Picard S, Lacroix P CURR OPIN INVESTIG DRUGS 2003 4 3 303-308
10. Modeling the 3D structure of GPCRs: Advances and application to drug discovery. Becker OM, Shacham S, Marantz Y, Noiman S CURR OPIN DRUG DISCOVERY DEV 2003 6 3 353-361
11. 1A receptor agonist PRX-00023 in a rodent model of attention-deficit/hyperactivity disorder. Zhang K, Moran-Gates T, Shacham S, Cho CR, Noiman S, Tarazi FI, Baldessarnini RJ ABSTR SOC NEUROSCI 2004 34 Abs 466.10 593827 TargetTalk - IBC Conference, Kinase and GPCR Targets, San Diego, CA, USA, 21-23 March 2005. Gilchrist A IDDB MEETING REPORT 2005 March 21-23
12. Predix starts PRX-00023 phase III anxiety trial. Predix Pharmaceuticals Inc PRESS RELEASE 2005 August 15
13. EPIX Pharmaceuticals: EPIX Pharmaceuticals Inc, Lexington, MA, USA (2006). www.predixpharm.com
14. 1- adrenoreceptors. Lopez-Roduez ML, Mocillo MJ, Fernandez E, Benhamu B, Teiada I, Avala D, Viso A, Campillo M, Delgado M, Manzanares J, Fuentes JA J MED CHEM 2005 48 7 2548-2558
15. 1A agonist (PRX-00023) for the treatment of anxiety and depression. Becker OM, Dhanoa DS, Marantz Y, Chen D, Shacham S, Cheruku S, Heifetz A, Mohanty P, Fichman M, Sharadendu A, Nudelman R, Kauffman M, Noiman S J MED CHEM 2006 49 11 3116-3135 • This study describes the discovery and synthesis of PRX-00023, and preclinical pharmacology and in silico modeling of GPCRs.
16. 1A agonist discovered in silico. Iyer GR, Donahue S, Potter S, Wang C, Oshana S, Kauffman M CLIN PHARMACOL THER 2006 79 2 69
17. 1A agonist discovered in silico is safe and well tolerated following multiple oral dose administration in healthy subjects. Iyer GR, Oshana S, Donahue S CLIN PHARMACOL THER 2006 79 2 45
18. 1A agonist discovered in silico in healthy subjects. Donahue S, Iyer GR, Oshana S, Kauffman M CLIN PHARMACOL THER 2006 79 2 18
19. 1A agonist in generalized anxiety disorder. Mathew S, Oshana S, Donahue S NEW CLIN DRUG EVAL UNIT ANNU MEET 2006 46 Abs I-13
20. EPIX and Predix Pharmaceuticals complete merger. EPIX Pharmaceuticals Inc PRESS RELEASE 2006 August 16
21. Molecular basis for regionally specific action of ethanol on γ-aminobutyric acid A receptors: Generalization to other ligand-gated ion channels. Criswell HE, Simson PE, Duncan GE, McCrown TJ, Herbert JS, Morrow AL, Breese GR J PHARMACOL EXP THER 1993 267 1 522-537
22. Benzodiazepine use, abuse, and dependence. O'Brien CP J CLIN PSYCHIAT 2005 66 Suppl 2 28-33
23. 1 binding sites as target for a novel putative anxiolytic. Dompert WU, Glaser T, Traber J NAUNYN SCHMIEDEBERGS ARCH PHARMACOL 1985 328 4 467-470
24. Gepirone. Organon. Leslie RA CURR OPIN INVESTIG DRUGS 2001 2 8 1120-1127
25. 1A receptor agonist. Lopez-Rodriguez ML, Rosado ML, Benhamu B, Morcillo MJ, Sanz AM, Orensanz L, Beneitez ME, Fuentes JA, Manzanares J J MED CHEM 1996 39 22 4439-4450
26. 1A receptor.
27. 1A receptors. Lopez-Rodriguez ML, Ayala D, Benhamu B, Morcillo MJ, Viso A CURR MED CHEM 2002 9 4 443-469 • A summary of the SAR of azapirones is provided.
28. G protein-coupled receptors: In silico drug discovery in 3D. Becker OM, Marantz Y, Shacham S, Inbal B, Heifetz A, Kalid O, Bar-Haim S, Warshaviak D, Fichman M, Noiman S PROC NATL ACAD SCI 2004 101 31 11304-11309 • A description of the successful use of PREDICT in rapid virtual screening in five different GPCRs.
29. 1A affinity/selectivity. Lopez-Rodriguez ML, Ayala D, Viso A, Benhamu B, Fernandez de la Pradilla R, Zarza F, Ramos JA BIOORG MED CHEM 2004 12 1551-1557
30. Modeling the 3D structure of GPCRs from sequence. Shacham S, Topf M, Avisar N, Glaser F, Marantz Y, Bar-Haim S, Noiman S, Naor Z, Becker OM MED RES REV 2001 21 5 472-483 • This paper describes the fundamentals of the PREDICT algorithm in non-rhodopsin drug-receptor docking experiments.
31. 2 receptor activity. Paluchowska MH, Bugno R, Bojarski AJ, Charakchieva-Mibnol S, Duszynska B, Tatarczynska E, Klodzinska A, Stachowicz K, Chojnacka-Wojcik E BIOORG MED CHEM 2005 13 4 1195-1200
32. 1A receptor ligands to explore the three-dimensional structure of the receptor. Lopez-Rodriguez ML, Vicente B, Deupi X, Barrondo S, Olivella M, Morcillo MJ, Behamu B, Ballesteros JA, Salles J, Pardo L MOL PHARMACOL 2002 62 1 15-21
33. Mouse model of hyperkinesis implicates SNAP-25 in behavioral regulation. Hess EJ, Collins KA, Wilson MC J NEUROSCI 1996 16 9 3104-3111
34. 1A adrenergic receptor. Evers A, Klabunde T J MED CHEM 2005 48 4 1088-1097
35. 1A receptor agonist. Lopez-Rodriguez ML, Morcillo MJ, Fernandez E, Benhamu B, Tejada I, Ayala D, Viso A, Olivella M, Pardo L, Delgado M, Manzanares J, Fuentes, JA BIOORG MED CHEM LETT 2003 13 8 1429-1432
36. 2 antagonist properties. Lopez-Rodriguez M, Morcillo MJ, Fernandez E, Porras E, Orensanz L, Beneytez E, Manzanares J, Fuentez JA J MED CHEM 2001 44 2 186-197
37. 3 receptors. Delgado M, Caicoya AG, Greciano V, Benhamu B, Lopez-Rodriguez ML, Fernandez-Alfonso MS, Pozo MA, Manzanares J, Fuentes JA EUR J PHARMACOL 2005 511 1 9-19
38. 2A serotonin receptors. Bronowska A, Les A, Chilmonczyk Z, Filipek S, Edvardsen O, Ostensen R, Sylte I BIOORG MED CHEM 2001 9 4 881-895
39. 1A receptor mediated. Oliver B, Zethof TJ, Ronken E, van der Heyden JA EUR J PHARMACOL 1998 342 2-3 177-182
40. 1-adrenoceptor antagonists prazosin, doxazosin, and terazosin. Thomas D, Wimmer AB, Wu K, Hammerling BC, Ficker EK, Kuyshey YA, Kiehn J, Katus HA, Schoels W, Karle CA NAUNYN SCHMIEDEBERGS ARCH PHARMACOL 2004 369 5 462-472
41. Kr) channel. Davie C, Pierre-Valentin J, Pollard C, Standen N, Mitcheson J, Alexander P, Thong B J CARDIOVASC ELECTROPHYSIOL 2004 15 11 1302-1309
42. New insights about HERG blockade obtain from protein modeling, potential energy mapping, and docking studies. Farid R, Day T, Friesner RA, Pearlstein RA BIOORG MED CHEM 2006 14 9 3160-3173
43. A phase II multicenter dose-finding, efficacy and safety trial of ipsapirone in outpatients with generalized anxiety disorder. Cutler NR, Hesselink JM, Sramek JJ PROG NEUROPSYCHPHARMACOL BIOL PSYCHIAT 1994 18 3 447-463
44. Generalized anxiety disorder: Treatment options. Sramek JJ, Zarotsky V, Cutler NR DRUGS 2002 62 11 1635-1648
45. Mixed results for EPIX's PRX-00023 in phase III anxiety trial. EPIX Pharmaceuticals Inc PRESS RELEASE 2006 September 21
46. 1A agonist, reduces ultrasonic vocalizations (USV) in infant rats selectively bred for high rates of vocalization. Branscomb A, Gannon KS, Shacham S, Chen D, Marantz Y, Becker O, Noiman S, Kauffman MG, Brunelli SA ABSTR SOC NEUROSCI 2006 Abs 290.24/OO71
47. Potential treatment paradigms for anxiety disorders. Millet B, Andre C, Deligne H, Olie J-P EXP OPIN INVESTIG DRUGS 1999 8 10 1589-1598
48. Psychosedative agents. 2. 8-(4-Substituted 1-piperazinylalkyl)-8- azaspiro[4,5]decane-7,9-diones. Wu Y-H, Rayburn JW, Allen LE, Ferguson HC, Kissel JW J MED CHEM 1972 15 5 477-479
49. 2-adrenoceptor blocking properties of buspirone and ipsapirone in healthy subjects. Relationship with the plasma concentration of the common metabolite 1-(2-pyrimidinyl)piperazine. Berlin I, Chalon S, Payan C, Schollnhammer G, Cesselin F, Varoquaux O, Puech AJ BR J CLIN PHARMACOL 1995 39 3 243-249
50. PREDICT. Modeling and in silico screening for G-protein coupled receptors. Shacham S, Marantz Y, Bar-Haim S, Kalid O, Warshaviak D, Avisar N, Becker OM PROTEINS 2004 57 1 51-86
51. PRX-00023 phase 3 top-line data: Investor conference call and webcast. EPIX Pharmaceuticals Inc COMPANY PRESENTATION 2006 September 22 1-12
52. Relapse prevention with gepirone ER in outpatients with major depression. Keller MB, Ruwe FJ, Janssens CJ, Sitsen JM, Jokinen R, Janczewski J J CLIN PSYCHOPHARMACOL 2005 25 1 79-84
53. Combined hERG channel inhibition and disruption of trafficking in drug-induced long QT syndrome by fluoxetine: A case-study in cardiac safety pharmacology. Hancox JC, Mitcheson JS BR J PHARMACOL 2006 149 5 457-459
54. Effect of 5-hydroxytryptophan on serum cortisol levels in major affective disorders. II. Relation to suicide, psychosis, and depressive symptoms. Meltzer HY, Perline R, Tricou BJ, Lowy M, Roberson A ARCH GEN PSYCHIAT 1984 41 4 379-387
55. Serotonin 5-HT receptor agonists as antidepressants: Pharmacological rationale and evidence for efficacy. Heiser JF, Wilcox CS CNS DRUGS 1998 10 5 343-353
56. 1A receptor using automated docking of bioactive compounds with defined geometry. Nowak M, Kolaczkowski M, Pawlowski M, Bojarski AJ J MED CHEM 2006 49 1 205-214
57. Pharmacokinetic-pharmacodynamic modeling of buspirone and its metabolite 1-(2-pyrimidinyl)-piperazine in rats. Zuideveld KP, Rusic-Pavletic J, Maas HJ, Peletier LA, Van der Graaf PH, Danhof M J PHARMACOL EXP THER 2002 303 3 1130-1137