Uptake of radioligands by rat heart and lung in vivo: CGP 12177 does and CGP 26505 does not reflect binding to beta-adrenoceptors

Eur J Pharmacol. 1992 Nov 3;222(1):107-12. doi: 10.1016/0014-2999(92)90469-k.

Abstract

The biodistribution of (-)-4-(3-t-butylamino-2-hydroxypropoxy)-[5,7-3H-benzimidazol-2-one (CGP12177, a non-selective beta-adrenoceptor antagonist) and 1-[2-(3-carbamoyl-4-hydroxy)-(5-3H-phenoxy)]-2-propanol methanesulfonate, (CGP26505, a beta 1-adrenoceptor antagonist) was studied in rats pretreated with various alpha- and beta-adrenoceptor blocking drugs (5 min before 3H injection, in dosages at which the drugs demonstrated the expected selectivity). Cardiac and pulmonary radioactivity were measured after 10 min, when specific binding was maximal. Uptake of [3H]CGP12177 was linked to binding to beta-adrenoceptors since it was not affected by prazosin or yohimbine, and was equally well inhibited by propranolol, unlabelled CGP12177 and isoprenaline. Moreover, atenolol and CGP20712A inhibited [3H]CGP12177 uptake in heart (predominantly beta 1-adrenoceptors) more potently than ICI 118,551, while in lungs (predominantly beta 2-adrenoceptors) ICI 118,551 was more potent than atenolol or CGP20712A. In contrast, [3H]CGP26505 uptake in the target organs was equally effectively inhibited by propranolol and ICI 118,551, and significantly lowered by alpha-adrenoceptor antagonists. We conclude that [11C]CGP12177, but not [11C]CGP2605 will be suitable for positron emission tomography imaging of beta-adrenoceptors in animals.

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology
  • Adrenergic beta-Antagonists / pharmacokinetics*
  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Imidazoles / pharmacokinetics*
  • In Vitro Techniques
  • Lung / metabolism*
  • Male
  • Myocardium / metabolism*
  • Propanolamines / pharmacokinetics*
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, beta / metabolism*
  • Tissue Distribution

Substances

  • Adrenergic alpha-Antagonists
  • Adrenergic beta-Antagonists
  • Imidazoles
  • Propanolamines
  • Receptors, Adrenergic, beta
  • CGP 20712A
  • CGP 12177