Tissue levels and displacement of in vivo labelled beta-adrenergic receptors by FM 24, an irreversible or slowly dissociable beta-blocker.

FM 24 [1-(2-exo-bicyclo[3,3,1]hept-2-ylphenoxy)-3-[(1-methylethyl)amino] 2-propanol hydrochloride] and propranolol were compared in mice with respect to their ability to displace in vivo 125I-hydroxybenzylpindolol which is selectively associated with beta-adrenergic receptor binding sites. After a simultaneous i.v. injection of the beta-blockers and 125I-hydroxybenzylpindolol propranolol was more active than FM 24. At an equiblocking dose i.e. a dose which inhibits by 80% the binding of 125I-hydroxybenzylpindolol, FM 24 was still effective after 6 h (40% inhibition in the brain and the heart, 60% in the lung) contrary to propranolol. After oral administration (2 mg/kg), 40% inhibition by FM 24 still persisted at 24 h in the heart whereas no effect of propranolol was detectable at 18 h. As the kinetics of [3H]FM 24 and [3H]propranolol after oral and i.v. administration are not very different we confirmed that the prolonged beta-blocking action of FM 24 was related to a tight irreversible binding to beta-receptors rather than to pharmacokinetic properties of this drug.