Effects of several putative beta 3-adrenoceptor agonists on lipolysis in human omental adipocytes.
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.


METHODS
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.


CONCLUSIONS
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.
Hoffstedt
J
J
Department of Medicine, Huddinge University Hospital, Karolinska Institute, Sweden.
Lönnqvist
F
F
Shimizu
M
M
Blaak
E
E
Arner
P
P
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology; D004149:Dioxoles / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects*; D009852:Omentum; D011412:Propanolamines / Q000494:pharmacology; D012694:Serine / Q000031:analogs & derivatives / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D002396:Catechols; D004149:Dioxoles; D004983:Ethanolamines; D011412:Propanolamines; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; C076952:SM 11044; D012694:Serine; C057368:BRL 37344; D007545:Isoproterenol; D005990:Glycerol; C033394:CGP 12177