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Titolo:
Positron emission tomography study of pindolol occupancy of 5-HT1A receptors in humans: Preliminary analyses
Autore:
Martinez, D; Mawlawi, O; Hwang, DR; Kent, J; Simpson, N; Parsey, RV; Hashimoto, T; Slifstein, M; Huang, YY; Van Heertum, R; Abi-Dargham, A; Caltabiano, S; Malizia, A; Cowley, H; Mann, JJ; Laruelle, M;
Indirizzi:
Columbia Univ, Coll Phys & Surg, Dept Psychiat & Radiol, New York, NY USA Columbia Univ New York NY USA , Dept Psychiat & Radiol, New York, NY USA SmithKline Beecham Pharmaceut, Addenbrookes Ctr Clin Invest, Cambridge, England SmithKline Beecham Pharmaceut Cambridge England est, Cambridge, England
Titolo Testata:
NUCLEAR MEDICINE AND BIOLOGY
fascicolo: 5, volume: 27, anno: 2000,
pagine: 523 - 527
SICI:
0969-8051(200007)27:5<523:PETSOP>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
PLACEBO-CONTROLLED TRIAL; SEROTONIN REUPTAKE INHIBITORS; IN-VIVO MICRODIALYSIS; MAJOR DEPRESSION; DOUBLE-BLIND; RAT-BRAIN; ANTIDEPRESSANT DRUGS; FLUOXETINE; COMBINATION; PAROXETINE;
Keywords:
5-HT1A receptors; positron-emission tomography; [C-11]WAY-100635; pindolol; SSRI; mood disorders;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Martinez, D New York State Psychiat Inst, Dept Neurosci, Div Brain Imaging, 1051 Riverside Dr,Box 42, New York, NY 10032 USA New York State Psychiat Inst 1051 Riverside Dr,Box 42 New York NY USA 10032
Citazione:
D. Martinez et al., "Positron emission tomography study of pindolol occupancy of 5-HT1A receptors in humans: Preliminary analyses", NUCL MED BI, 27(5), 2000, pp. 523-527

Abstract

Preclinical studies in rodents suggest that augmentation of serotonin reuptake inhibitors (SSRIs) therapy by the 5-hydroxytryptamine(1A) (5-HT1A) receptor agent pindolol might reduce the delay between initiation of treatmentand antidepressant response. This hypothesis is based on the ability of pindolol to potentiate the increase in serotonin (5-HT) transmission induced by SSRIs, an effect achieved by blockade of the 5-HT1A autoreceptors in thedorsal raphe nuclei (DRN). However, placebo-controlled clinical studies ofpindolol augmentation of antidepressant therapy have reported inconsistentresults. Here, we evaluated the occupancy of 5-HT1A receptors following treatment with controlled release pindolol in nine healthy volunteers with positron-emission tomography (PET). Each subject was studied four times: at baseline (scan 1), following 1 week of oral administration of pindolol CR (7.5 mg/day) at peak level, 4 h after the dose (scan 2), and at 10 h following the dose (scan 3), and following one dose of pindolol CR (30 mg) (at peaklevel, 4 h) (scan 4). Pindolol occupancy of 5-HT1A receptors was evaluatedin the DRN and cortical regions as the decrease in binding potential (BP) of the radiolabelled selective 5-HT1A antagonist [carbonyl-C-11]WAY-100635 or [carbonyl-C-11] N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)-N-(2-pyridyl)cyclohexanecarboxamide abbreviated as [C-11]WAY-100635. Pindolol dose-dependently decreased [C-11]WAY-100635 BP. Combining all the regions, occupancy was 20 +/- 8% at scan 2, 14 +/- 8% at scan 3, and 44 +/- 8% at scan 4 The results of this study suggest that at doses used in clinical studies of augmentation of the SSRI effect by pindolol (2.5 mg t.i.d.), the occupancy of 5-HT1A receptors is moderate and highly variable between subjects. This factormight explain the variable results obtained in clinical studies. On the other hand, at each dose tested, pindolol occupancy of 5-HT1A receptors was higher in the DRN compared to cortical regions, demonstrating a significant in vivo selectivity for DRN 5-HT1A autoreceptors relative to cortico-limbicpostsynaptic receptors. This selectivity is necessary for the potentiationof 5-HT transmission, and this finding represents an important proof of concept in the development of 5-HT1A agents for this application. Early evaluation of new drugs with PET imaging will enable rapid screening of compounds based on DRN selectivity and more appropriate determination of doses for clinical trials. NUCL MED BIOL 27;5: 523-527, 2000. (C) 2000 Elsevier Science Inc. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/01/20 alle ore 16:52:14