Tolerability, pharmacokinetics, and neuroendocrine effects of PRX-00023, a Novel 5-HT1A agonist, in healthy subjects

Journal of Clinical Pharmacology

Volumn 47, Issue 7, 2007, Pages 817-824

  Iyer, Ganesh R ^a   Reinhard Jr , John F ^a   Oshana, Scott ^a   Kauffman, Michael ^a   Donahue, Stephen ^a  

^a Epix Pharmaceuticals   (United States)

Author keywords

5 HT1A; Affective disorders; Pharmacokinetics (PK) and pharmacodynamics (PD); Phase I; PRX 00023; Serotonin

Indexed keywords

N [3 [4 [4 (CYCLOHEXYLMETHYLSULFONAMIDO)BUTYL] 1 PIPERAZINYL]PHENYL]ACETAMIDE; PLACEBO; PROLACTIN; ANTIDEPRESSANT AGENT; 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;

ADULT; AGED; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DIARRHEA; DIZZINESS; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG DOSE INCREASE; DRUG DOSE TITRATION; DRUG EFFECT; DRUG ELIMINATION; DRUG FATALITY; DRUG HALF LIFE; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FEMALE; HEADACHE; HUMAN; HUMAN EXPERIMENT; LOOSE FECES; MALE; NAUSEA; NORMAL HUMAN; POSITIONAL DIZZINESS; PROLACTIN BLOOD LEVEL; SINGLE DRUG DOSE; ADOLESCENT; BLOOD; CLINICAL TRIAL; COHORT ANALYSIS; DOUBLE BLIND PROCEDURE; DRUG POTENTIATION; HALF LIFE TIME; MIDDLE AGED; PHASE 1 CLINICAL TRIAL;

ADOLESCENT; ADULT; ANTIDEPRESSIVE AGENTS; COHORT STUDIES; DOUBLE-BLIND METHOD; FEMALE; HALF-LIFE; HUMANS; MALE; MIDDLE AGED; PIPERAZINES; PROLACTIN; RECEPTOR, SEROTONIN, 5-HT1A; SULFONAMIDES;

EID: 34548024383     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1177/0091270007300953     Document Type: Article

References (16)

1. Becker OM, Dhanoa DS, Marantz Y, et al. An integrated in silico 3D model-driven discovery of a novel, potent and selective amidosulfonamide 5HT1A agonist (PRX-00023) for the treatment of anxiety and depression. J Med Chem. 2006;49:3116-3135.
2. Norman S. The use of buspirone in psychiatry. J. Clin Psychiatry. 1994;12:3-10.
3. Blier P. The pharmacology of putative early-onset antidepressant strategies. Eur Neuropsychopharmacol. 1986;3:57-66.
4. Leslie RA. Gepirone: organon. Curr Opin Investig Drugs. 2001; 2:1120-1127.
5. Gammans RE, Mayol RF, LaBudde JA. Metabolism and disposition of buspirone. Am ) Med. 1986;80(3B):41-51.
6. BuSpar [package insert]. New York: Bristol-Myers Squibb; 2002.
7. Terron JA, Ramirez-San Juan E, Hong E, Villalon CM. Role of alpha1-adrenoceptors in the reduction of external carotid blood flow induced by buspirone and ipsapirone in the dog. Life Sci. 1996;58:63-73.
8. 8.NemeroffC.Anxiolytics:past,present,andfutureagents.JClinPsychiatry. 2003;64(suppl3):3-6.(Pubitemid36389865)
9. Silvio C, Ivana C, Gianluigi V, Silvio G. 1-(2-pyrimidinyl) piperazine as active metabolite of buspirone in man and rat. Pharmacology. 1986;33:46-51.
10. 10.BarbhaiyaRH,ShuklaUA,PfefferM,etal. Dispositionkineticsofbuspironeinpatients withrenalorhepaticimpairmentafteradministrationofsingleandmultipledoses. EurJClinPharmacol.1994;46:41-47.(Pubitemid24067587)
11. Gammans R, Mayol R, LaBudde J. Metabolism and disposition of buspirone. Am J Med. 1986;80:41-51.
12. 12. Mahmood I, Sahajwalla C. Clinical pharmacokinetics and pharmacodynamics of buspirone, an anxiolytic drug. Clin Pharmacokinet. 1999;36:277-287. (Pubitemid 29201736)
13. 13. Blier P, Bergeron R, de Montigny C. Selective activation of postsynaptic 5-HT1A receptors induces rapid antidepressant response. Neuropsychopharmacology. 1997;16:333-338. (Pubitemid 27211731)
14. Ree Larsen P, Kronenberg H, Melmed S, Polonsky K. Williams Textbook of Endocrinology. 10th ed. New York: Elsevier; 2002.
15. Serri O, Chik CL, Ehud Ur, Ezzat S. Diagnosis and management of hyperprolactinemia. CMAJ. 2003;169:575-581.
16. 16. Bridge MW, Marvin G, Thompson CE, Sharma A, Jones DA, Kendall MJ. Quantifying the 5-HT1A agonist action of buspirone in man. Psychopharmcology. 2001;158:224-229. (Pubitemid 33071159)