DISTRIBUTION OF THE MUSCARINIC ACETYLCHOLINE-RECEPTOR ANTAGONISTS, QUINUCLIDINYL BENZILATE AND QUINUCLIDINYL BENZILATE METHIODIDE (BOTH TRITIATED), IN RAT, GUINEA-PIG, AND RABBIT

Abstract

The distribution of [3H]quinuclidinyl benzilate and its methiodide salt was determined in rat, guinea pig and rabbit. Accumulation in the myocardium of up to 2% of the injected dose per gram of tissue was obtained with both compounds, providing heart-to-blood ratios of .apprx. 30 and heart-to-lung ratios of .apprx. 4. The accumulation in the heart was blocked (89%) by preinjection of atropine. The distribution of 3H in rabbit heart corresponds to the muscarinic receptor densities determined in vitro. Calculation of the theoretical maximum for the bound-to-free ratio, based on in-vitro equilibrium binding isotherms, caused ratios in reasonable agreement with the experimental results. The high accumulation in the heart with low serum concentration suggests that the methiodide salt of quinuclidinyl benzilate represents an ideal parent structure for the design of a receptor-binding .gamma.-emitting radiopharmaceutical for imaging of the myocardium.