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.
Jasper
J R
JR
Department of Pharmacology, University of California San Diego, La Jolla 92093.
Michel
M C
MC
Insel
P A
PA
D002354:Carteolol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D008223:Lymphoma / Q000378:metabolism; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D013566:Sympathomimetics; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D013566:Sympathomimetics; C060345:8-hydroxycarteolol; D002354:Carteolol; D000242:Cyclic AMP; D007545:Isoproterenol