Add time:07/14/2019         Source:sciencedirect.com

Prodrugs of isoproterenol, 3-O-,4-O-diacetylisoproterenol (DAI) and 3-O-,4-O-dibenzoylisoproterenol (DBI), were tested for effects on colonic temperature in mice. Intraperitoneal injections of DAI or DBI (20, 50 and 125 μmol/kg) produced a dose-related hypothermia. Isoproterenol (125 μmol/kg) and its metabolite, 3-O-methylsoproterenol (125 μmol/kg), caused hypothermia of a lesser intensity. The involvement of β-adrenergic receptors in the hypothermic effect of DAI (50 μmol/kg) was established by pretreatments with propranolol and sotalol. The results are discussed in terms of the pharmacodynamics of prodrugs, the pharmacokinetics and mechanism of action of isoproterenol, and the possible role of β-receptors in temperature regulation. DAI and DBI may be useful as prodrugs for the activation of central β-receptors.

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