In vivo receptor binding of iodinated beta-adrenoceptor blockers.
Six radiolabeled beta-adrenoceptor blocking agents with a range of affinity constants were evaluated as radioindicators for adrenoceptors in guinea-pig heart and lung. All concentrated in the heart and lung at levels in excess of 0.1% dose/g tissue. On the basis of displacement studies using propranolol, two of the six compounds showed beta-adrenoceptor binding in the lung, and one, H-3 carazolol, showed receptor binding in the heart. These results agree qualitatively with a bi-molecular reversible equilibrium model, and suggest that the beta-adrenoceptor blockers as a group will not be useful in vivo probes of receptor concentration in the heart because of the low affinity constants and high levels of nonreceptor binding associated with the present-day clinical beta blockers. Beta-adrenoceptor blocking agents with affinity constants in excess of 10(9) will be needed to give heart-to-blood ratios of 10.
D000319:Adrenergic beta-Antagonists / Q000378:metabolism*; D000526:Alprenolol / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D002227:Carbazoles / Q000378:metabolism; D004082:Dihydroalprenolol / Q000378:metabolism; D006168:Guinea Pigs; D007457:Iodine Radioisotopes; D002040:Levobunolol / Q000031:analogs & derivatives / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011217:Practolol / Q000031:analogs & derivatives / Q000378:metabolism; D011335:Proadifen / Q000494:pharmacology; D011412:Propanolamines / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
C024559:4-hydroxyphenethylamino-3-(1-oxotetrahydronaphthaloxy)propan-2-ol; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D007457:Iodine Radioisotopes; D011412:Propanolamines; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; C014382:carazolol; D004082:Dihydroalprenolol; C024557:4-hydroxyphenethylamino-3-(4-acetamido)phenoxypropan-2-ol; C024558:4-hydroxyphenethylamino-3-(2-allyl)phenoxypropan-2-ol; D000526:Alprenolol; D011433:Propranolol; D011335:Proadifen; D002040:Levobunolol; D011217:Practolol