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Titolo:
Affinity of (+/-)-pindolol, (-)-penbutolol, and (-)-tertatolol for pre- and postsynaptic serotonin 5-HT1A receptors in human and rat brain
Autore:
Castro, ME; Harrison, PJ; Pazos, A; Sharp, T;
Indirizzi:
Univ Oxford, Radcliffe Infirm, Dept Clin Pharmacol, Oxford OX2 6HE, England Univ Oxford Oxford England OX2 6HE in Pharmacol, Oxford OX2 6HE, England Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford, England Univ Oxford Oxford England rneford Hosp, Dept Psychiat, Oxford, England Univ Cantabria, Dept Physiol & Pharmacol, E-39005 Santander, Spain Univ Cantabria Santander Spain E-39005 armacol, E-39005 Santander, Spain
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 2, volume: 75, anno: 2000,
pagine: 755 - 762
SICI:
0022-3042(200008)75:2<755:AO((A(>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
PLACEBO-CONTROLLED TRIAL; ANTIDEPRESSANT-LIKE ACTIVITY; IN-VIVO MICRODIALYSIS; H-3 WAY-100635; DOUBLE-BLIND; PINDOLOL AUGMENTATION; REUPTAKE INHIBITORS; EXTRACELLULAR 5-HT; MAJOR DEPRESSION; ANTAGONIST;
Keywords:
serotonin 5-HT1A receptors; beta-adrenoceptors; [H-3]WAY-100635; pindolol; penbutolol; tertatolol;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Sharp, T Univ Oxford, Dept Pharmacol, Mansfield Rd, Oxford OX1 3QT, England Univ Oxford Mansfield Rd Oxford England OX1 3QT OX1 3QT, England
Citazione:
M.E. Castro et al., "Affinity of (+/-)-pindolol, (-)-penbutolol, and (-)-tertatolol for pre- and postsynaptic serotonin 5-HT1A receptors in human and rat brain", J NEUROCHEM, 75(2), 2000, pp. 755-762

Abstract

There is considerable interest in the use of drugs that selectively block presynaptic (somatodendritic) serotonin 5-HT1A receptors for the adjunctivetreatment of major depressive disorder. The 5-HT1A/beta-adrenoceptor ligands (+/-)-pindolol, (-)-tertatolol, and (-)-penbutolol are currently under clinical investigation, and knowledge of their affinity at different populations of central 5-HT1A receptors is needed. Here we have determined the affinity of these drugs for presynaptic and postsynaptic 5-HT1A receptors in postmortem human and rat brain using receptor autoradiography and the selective 5-HT1A radioligand [H-3]WAY-100635. The binding of [H-3]WAY-100635 was specific and saturable and showed high affinity in the rat dorsal raphe nucleus and hippocampus (K-D = 1.5-1.7 nM). In competition studies, the three compounds had nanomolar affinity and produced monophasic displacement of [H-3]WAY-100635 binding in all regions of both species. (-)-Penbutolol and (-)-tertatolol had similar affinity for pre- and postsynaptic 5-HT1A receptors in both rat and human brain. However, in the human, but not the rat, the affinity of (+/-)-pindolol in dorsal raphe nucleus (K-i = 8.9 +/- 1.1 nM) was slightly but significantly higher than that in hippocampus (K-i = 14.4 +/- 1.5 n/M in CA1). In summary, our data show that (+/-)-pindolol, (-)-tertatolol, and (-)-penbutolol are all high-affinity ligands at native human and rat 5-HT1A receptors. (-)-Penbutolol and (-)-tertatolol do not discriminate between the pre- and postsynaptic 5-HT1A sites tested in either species,but (+/-)-pindolol showed a slightly higher affinity for the presynaptic site in human brain. Further work is needed to establish whether the latter difference is clinically relevant.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/07/20 alle ore 20:52:44