3-O-,4-O-diacetylisoproterenol and 3-O-,4-O-dibenzoylisoproterenol: hypothermic effects in mice and the involvement of beta-adrenergic receptors

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 mumol/kg) produced a dose-related hypothermia. Isoproterenol (125 mumol/kg) and its metabolite, 3-O-methylisoproterenol (125 mumol/kg), caused hypothermia of a lesser intensity. The involvement of beta-adrenergic receptors in the hypothermic effect of DAI (50 mumol/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 beta-receptors in temperature regulation. DAI and DBI may be useful as prodrugs for the activation of central beta-receptors.