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C 3-Professur f. Klinische Pharmakologie
Versbacher Str. 9, 97078 Würzburg Mail: graefe@toxi.uni-wuerzburg.de Url: |
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Research foci (and basic equipment-based research projects):
On the Pharmacology of m-iodobenzylguanidine (MIBG).
Despite the widespread use of MIBG in clinical oncology and cardiology, there is paucity of published data on the pharmacology of MIBG. We have previously shown that MIBG has tyramine-like actions in vitro. Therefore, one goal of the present study was to determine how the indirect-sympathomimetic actions of MIBG compare with those of tyramine in vivo. The similarity of the chemical structure of MIBG to that of gunethidine led to the hypothesis that MIBG acts like an adrenergic neurone blocking agent. This working hypothesis has never been verified experimentally. Therefore, another goal of the present study was to determine whether MIBG blocks the nerve stimulation-induced release of noradrenaline and whether MIBG, like many other adrenergic neurone blocking drugs, inhibits monoamine oxidase.
Results:
The results show that MIBG behaves in vitro and in vivo like an indirectly acting sympathomimetic drug, i.e. it acts like tyramine (Graefe et al. 1999). Moreover, MIBG inhibits the exocytotic release of noradrenaline induced by electrical stimulation (Bossle et al. 2002). Though being a preferential inhibitor of monoamine oxidase type A, MIBG blocks both isoforms of monoamine oxidase. In the intact heart, MIBG was 1000 times more potent in inhibiting monoamine oxidase type A than in cell-free heart homogenates. Hence, MIBG is transported into cardiac sympathetic nerves against a concentration gradient of 1000:1 (Bossle et al. 2002).
Literatur:
Graefe et al. Sympathomimetic effects of MIBG: comparison with tyramine. J Nucl Med 1999; 40:1342-1351.
Bossle et al. Meta-iodobenzylguanidine acts as adrenergic neurone blocking drug and inhibits monoamine oxidase. Naunyn-Schhmiedeberg´s Arch Pharmacol 2002, submitted.