Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Sympathomimetic effects of MIBG: Comparison with tyramine
Autore:
Graefe, KH; Bossle, F; Wolfel, R; Burger, A; Souladaki, M; Bier, D; Dutschka, K; Farahati, J; Bonisch, H;
Indirizzi:
Univ Wurzburg, Dept Pharmacol, D-97078 Wurzburg, Germany Univ Wurzburg Wurzburg Germany D-97078 rmacol, D-97078 Wurzburg, Germany Univ Wurzburg, Dept Nucl Med, Wurzburg, Germany Univ Wurzburg Wurzburg Germany rzburg, Dept Nucl Med, Wurzburg, Germany Univ Essen Gesamthsch, Dept Nucl Med, Essen, Germany Univ Essen Gesamthsch Essen Germany hsch, Dept Nucl Med, Essen, Germany Univ Bonn, Dept Pharmacol, D-5300 Bonn, Germany Univ Bonn Bonn Germany D-5300 Bonn, Dept Pharmacol, D-5300 Bonn, Germany
Titolo Testata:
JOURNAL OF NUCLEAR MEDICINE
fascicolo: 8, volume: 40, anno: 1999,
pagine: 1342 - 1351
SICI:
0161-5505(199908)40:8<1342:SEOMCW>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
SK-N-SH; I-131 METAIODOBENZYLGUANIDINE; M-IODOBENZYLGUANIDINE; RAT-HEART; CELLS; NOREPINEPHRINE; I-123; PHEOCHROMOCYTOMA; PHARMACOKINETICS; NEUROBLASTOMA;
Keywords:
metaiodobenzylguanidine; tyramine; indirect sympathomimetic action; neuronal uptake; vesicular monoamine transporter;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Graefe, KH Univ Wurzburg, Dept Pharmacol, Versbacher Str 9, D-97078 Wurzburg, Germany Univ Wurzburg Versbacher Str 9 Wurzburg Germany D-97078 ermany
Citazione:
K.H. Graefe et al., "Sympathomimetic effects of MIBG: Comparison with tyramine", J NUCL MED, 40(8), 1999, pp. 1342-1351

Abstract

Because nothing is known about whether metaiodobenzylguanidine (MIBG) has tyramine-like actions, the sympathomimetic effects of MIBG were determined in the isolated rabbit heart and compared with those of tyramine. Methods: Spontaneously beating rabbit hearts were perfused with Tyrode's solution (Langendorff technique; 37 degrees C; 26 mL/min), and the heart rate as well as the norepinephrine and dopamine overflow into the perfusate was measuredbefore and after doses of MIBG or tyramine (0.03-10 mu mol) given as bolusinjections (100 mu L) into the aortic cannula. K-m and V-max values for the neuronal uptake (uptake(1)) of I-125-MIBG and C-14-tyramine were obtainedin human neuroblastoma (SK-N-SH) cells. The K-i of MIBG for inhibition of the H-3-catecholamine uptake mediated by the vesicular monoamine transporter was determined in membrane vesicles obtained from bovine chromaffin granules and compared with the previously reported K-i value for tyramine determined under identical experimental conditions. Results: By producing increases in heart rate and norepinephrine overflow, both compounds had dose-dependent sympathomimetic effects in the rabbit heart. MIBG was much less effective than tyramine in increasing heart rate (maximum effect 59 versus 156 beats/min) and norepinephrine overflow (maximum effect 35 versus 218 pmol/g). Tyramine also caused increases in dopamine overflow, whereas MIBG was a poor dopamine releaser. At a dose of 10 mu mol, the increase in heart rate lasted more than 60 min after MIBG and about 20 min after tyramine injection. Accordingly, the norepinephrine overflow caused by 10 mu mol MIBG and tyramine declined with half-lives of 57.8 and 2.2 min, respectively. The effects of both drugs were drastically reduced in hearts exposed to 2 mu mol/L desipramine. The kinetic parameters characterizing the saturation of neuronaluptake by I-125-MIBG and C-14-tyramine were similar for the two compounds:K-m values of MIBG and tyramine were 1.6 and 1.7 mu mol/L, respectively, and V-max values of MIBG and tyramine were 43 and 37 pmol/mg protein/min, respectively. However, in inhibiting the vesicular H-3-catecholamine uptake, MIBG was eight times less potent than tyramine. Conclusion: MIBG is much less effective than tyramine as an indirect sympathomimetic agent. This is probably a result of its relatively low affinity for the vesicular monoamine transporter and explains the relatively poor ability of the drug to mobilize norepinephrine stored in synaptic vesicles. The long duration of MIBG action results primarily from the drug not being metabolized by monoamine oxidase. The sympathomimetic effects of MIBG described here are not likely to come into play in patients given diagnostic or common therapeutic doses of radioiodinated MIBG.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 11:23:49