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Titolo:
Monoamine oxidase inhibition is unlikely to be relevant to the risks associated with phentermine and fenfluramine: a comparison with their abilities to evoke monoamine release
Autore:
Kilpatrick, IC; Traut, M; Heal, DJ;
Indirizzi:
Knoll Ltd, Res & Dev, Nottingham NG1 7AR, England Knoll Ltd Nottingham England NG1 7AR & Dev, Nottingham NG1 7AR, England Knoll GmbH, D-67061 Ludwigshafen, Germany Knoll GmbH Ludwigshafen Germany D-67061 H, D-67061 Ludwigshafen, Germany
Titolo Testata:
INTERNATIONAL JOURNAL OF OBESITY
fascicolo: 10, volume: 25, anno: 2001,
pagine: 1454 - 1458
SICI:
0307-0565(200110)25:10<1454:MOIIUT>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
PRIMARY PULMONARY-HYPERTENSION; SIBUTRAMINE HYDROCHLORIDE; EXTRACELLULAR DOPAMINE; VALVULAR ABNORMALITIES; NUCLEUS-ACCUMBENS; FLUOXETINE PROZAC; PLASMA SEROTONIN; RAT-BLOOD; IN-VITRO; DRUGS;
Keywords:
phentermine; fenfluramine; monoamine oxidase; serotonin reuptake; serotonin release; cardiovascular;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Kilpatrick, IC Knoll Ltd, Res & Dev, St Nicholas Court,25-27 Castle Gate, Nottingham NG1 7AR, England Knoll Ltd St Nicholas Court,25-27 Castle Gate Nottingham England NG1 7AR
Citazione:
I.C. Kilpatrick et al., "Monoamine oxidase inhibition is unlikely to be relevant to the risks associated with phentermine and fenfluramine: a comparison with their abilities to evoke monoamine release", INT J OBES, 25(10), 2001, pp. 1454-1458

Abstract

OBJECTIVE AND DESIGN: It has been proposed that the anti-obesity agent, phentermine, may act in part via inhibition of monoamine oxidase (MAO). The ability of phentermine to inhibit both MAO(A) and MAO(B) in vitro has been examined along with that of the fenfluramine isomers, a range of selective serotonin reuptake inhibitors and sibutramine and its active metabolites. RESULTS: In rat brain, harmaline and lazabemide showed potent and selective inhibition of MAO(A) and MAO(B), their respective target enzymes, with IC50 values of 2.3 and 18 nM. In contrast, all other drugs examined were onlyweak inhibitors of MAO(A) and MAO(B) with IC50 values for each enzyme in the moderate to high micromolar range. For MAO(A), the IC50 for phentermine was estimated to be 143 muM, that for S(+)-fenfluramine, 265 muM and that for sertraline, 31 muM. For MAO(B), example IC(50)s were as follows: phentermine (285 muM), S(+)-fenfluramine (800 muM) and paroxetine (16 muM). Sibutramine was unable to inhibit either enzyme, even at its limit of solubility. CONCLUSION: We therefore suggest that MAO inhibition is unlikely to play arole in the pharmacodynamic properties of any of the tested drugs, including phentermine. Instead, the lack of potency of these drugs as MAO inhibitors is contrasted with their powerful ability either to inhibit the uptake of one or more monoamines (fluoxetine, paroxetine, sertraline, sibutramine'sactive metabolites) or to evoke the release of one or more monoamines (S(+)-fenfluramine, S(+)-norfenfluramine, phentermine). These differences in mode of action may be linked to the adverse cardiovascular events experiencedwith some of the releasing agents.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 22:42:18