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Titolo:
beta-blocker binding to human 5-HT1A receptors in vivo and in vitro: Implications for antidepressant therapy
Autore:
Rabiner, EA; Gunn, RN; Castro, ME; Sargent, PA; Cowen, PJ; Koepp, MJ; Meyer, JH; Bench, CJ; Harrison, PJ; Pazos, A; Sharp, T; Grasby, PM;
Indirizzi:
Hammersmith Hosp, MRC, Cyclotron Unit, Imperial Coll Sch Med, London W12 0NN, England Hammersmith Hosp London England W12 0NN Sch Med, London W12 0NN, England Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford, England Univ Oxford Oxford England rneford Hosp, Dept Psychiat, Oxford, England Univ Oxford, Radcliffe Infirm, Dept Clin Pharmacol, Oxford OX2 6HE, England Univ Oxford Oxford England OX2 6HE in Pharmacol, Oxford OX2 6HE, England Charing Cross Hosp, Div Neurosci & Psychol Med, Imperial Coll Sch Med, London, England Charing Cross Hosp London England mperial Coll Sch Med, London, England Univ Cantabria, Dept Physiol & Pharmacol, E-39005 Santander, Spain Univ Cantabria Santander Spain E-39005 armacol, E-39005 Santander, Spain Univ Toronto, Dept Psychiat, PET Ctr, Clarke Inst Psychiat, Toronto, ON, Canada Univ Toronto Toronto ON Canada Clarke Inst Psychiat, Toronto, ON, Canada
Titolo Testata:
NEUROPSYCHOPHARMACOLOGY
fascicolo: 3, volume: 23, anno: 2000,
pagine: 285 - 293
SICI:
0893-133X(200009)23:3<285:BBTH5R>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
PLACEBO-CONTROLLED TRIAL; SEROTONIN REUPTAKE INHIBITORS; RAT-BRAIN; DOUBLE-BLIND; MAJOR DEPRESSION; IN-VIVO; AUTORECEPTOR BLOCKADE; PINDOLOL AUGMENTATION; FRONTAL-CORTEX; RAPHE NUCLEI;
Keywords:
human 5-HT1A receptor; positron emission tomography; pindolol; autoradiography; antidepressant drugs;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
56
Recensione:
Indirizzi per estratti:
Indirizzo: Rabiner, EA Hammersmith Hosp, MRC, Cyclotron Unit, Imperial Coll Sch Med, Du Cane Rd, London W12 0NN, England Hammersmith Hosp Du Cane Rd London England W12 0NN N, England
Citazione:
E.A. Rabiner et al., "beta-blocker binding to human 5-HT1A receptors in vivo and in vitro: Implications for antidepressant therapy", NEUROPSYCH, 23(3), 2000, pp. 285-293

Abstract

A novel strategy for improving the treatment of depressive illness is augmentation of antidepressants with a 5-HT1(1A) autoreceptor antagonist. However, trials using the 5-HT1(1A)/beta-blocker pindolol are proving inconsistent. We report how positron emission tomography (PET) and in vitro autoradiography can inform trials of antidepressant augmentation. We show that in healthy volunteers, in vivo, pindolol (n = 10) and penbutolol (n = 4), but not tertatolol (n = 4) occupy the human 5-HT1A receptors, at clinical doses. Pindolol, as well as the beta-blockers penbutolol and tertatolol, has high affinity for human 5-HT1A receptors in post-mortem brain slices (n = 4). Pindolol shows preference for 5-HT1A autoreceptors versus the post-synaptic receptors both in vitro and in vivo. Our data reveal that pindolol doses used in antidepressant trials so far are suboptimal for significant occupancy at the 5-HT1A autoreceptor. Penbutolol or higher doses of pindolol are candidates for testing as antidepressant augmenting regimes in future clinical trials. (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. All rights reserved.

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Documento generato il 29/03/20 alle ore 00:42:48