The beta-adrenoceptor antagonist carteolol and its metabolite 8-hydroxycarteolol have different intrinsic sympathomimetic activities.

We have tested the effects of carteolol and 8-hydroxycarteolol on cAMP generation in S49 lymphoma and BC3H1 smooth muscle-like cells. Carteolol was a high affinity beta-adrenoceptor antagonist in both systems but did not stimulate cAMP accumulation. The metabolite 8-hydroxycarteolol also was a high affinity antagonist. In contrast to its parent compound, however, it possessed an agonistic component which was considerably stronger than that of other beta-adrenoceptor blockers with intrinsic sympathomimetic activity, e.g. dichloroisoprenaline, pindolol, or celiprolol. These results suggest that metabolites can possess different pharmacodynamic properties in terms of beta-adrenoceptor interaction relative to parent compounds.