BACKGROUND: Atypical beta 3-adrenoceptor agonists have attained an increasing interest as potential drugs against obesity and diabetes. However, their pharmacological actions on the native, human beta 3-adrenoceptor are not well defined. DESIGN: In the present study, the lipolytic effects of several putative beta 3-adrenoceptor agonists were investigated in human omental adipocytes. RESULTS: CL 316 243 and CGP 12177 had selective partial beta 3-agonist effects (pD2 about 4 and 8, respectively); the latter drug is a beta 1-/beta 2-adrenoceptor blocker in addition to its beta 3-adrenoceptor agonist activity. BRL 37344 and SM 11044 were also partial agonists, but with significant beta 1- and/or beta 2-adrenoceptor agonist properties. Bucindolol, ZD 2079, ICI D7114 and SR 58611A were ineffective as lipolytic drugs. In addition, ICI D7114 was a non-selective beta 1-/beta 2-/beta 3-adrenoceptor antagonist in human adipocytes. CONCLUSION: None of the beta 3-adrenoceptor agonists tested is an ideal drug for therapeutic use in man (i.e. regarded as a selective and full agonist with high receptor potency). Only CL 316 243 may have a potential therapeutic role, although the potency is very low. CGP 12177 is useful as a reference substance for human in vitro studies.
BACKGROUND: Atypical beta 3-adrenoceptor agonists have attained an increasing interest as potential drugs against obesity and diabetes. However, their pharmacological actions on the native, humanbeta 3-adrenoceptor are not well defined. DESIGN: In the present study, the lipolytic effects of several putative beta 3-adrenoceptor agonists were investigated in human omental adipocytes. RESULTS: CL 316 243 and CGP 12177 had selective partial beta 3-agonist effects (pD2 about 4 and 8, respectively); the latter drug is a beta 1-/beta 2-adrenoceptor blocker in addition to its beta 3-adrenoceptor agonist activity. BRL 37344 and SM 11044 were also partial agonists, but with significant beta 1- and/or beta 2-adrenoceptor agonist properties. Bucindolol, ZD 2079, ICI D7114 and SR 58611A were ineffective as lipolytic drugs. In addition, ICI D7114 was a non-selective beta 1-/beta 2-/beta 3-adrenoceptor antagonist in human adipocytes. CONCLUSION: None of the beta 3-adrenoceptor agonists tested is an ideal drug for therapeutic use in man (i.e. regarded as a selective and full agonist with high receptor potency). Only CL 316 243 may have a potential therapeutic role, although the potency is very low. CGP 12177 is useful as a reference substance for human in vitro studies.