Potential anti-diabetic applications of a new molecule with affinity for beta 3-adrenoceptors.
beta 3-adrenoceptors have been described through both molecular and pharmacological studies. In this context, it has been characterized the beta 3-adrenoceptor agonist activity of a new compound (Trecadrine), and evaluated whether it exhibits additional activity at beta 1- and beta 2-adrenoceptor subtypes. In addition, it has been tested its potential anti-diabetic properties in a model of alloxan-induced diabetes in rats. Our data show that Trecadrine induces oesophageal muscularis mucosae relaxation, indicating a putative action on beta 3-adrenoceptors. In the absence of beta 3-adrenoceptor antagonists, assays with beta 1- and beta 2-adrenergic antagonists reveal a quite remarkable selectivity for beta 3-adrenoceptors. Furthermore, it has been suggested that this molecule has hypoglycaemic and lipomobilizing effects, although hypoglycaemia was not related to an increase in insulin secretion in diabetic rats. It is concluded that Trecadrine mainly acts through beta 3-adrenoceptors, and it may constitute a potential drug in the treatment of diabetes.
Barrionuevo
M
M
Department of Pharmacology, University of Navarra, Pamplona, Spain.
Milagro
F I
FI
Cenarruzabeitia
E
E
Martínez
J A
JA
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001592:Benzyl Alcohols / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004947:Esophagus / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D001592:Benzyl Alcohols; D001786:Blood Glucose; D007093:Imidazoles; D007328:Insulin; D011412:Propanolamines; D014280:Triglycerides; C101319:trecadrine; C026777:ICI 118551; C049763:CGP 20712A