In vivo effect of methyl-quinuclidinyl-benzylate on myocardial beta-adrenoceptor density.

The muscarinic receptor antagonist methyl-quinuclidinyl-benzylate decreased myocardial beta-adrenoceptor density Bmax: 20.4 +/- 2.4 pmol/ml tissue versus 33.3 +/- 4 pmol/ml tissue in control dogs (P < 0.001), as assessed by using [11C]CGP-12177 (((2S)-4-(3-t-butyl-amino-2 hydroxypropoxy)-benzimidazol-2-one)) and positron emission tomography. In contrast, atropine did not induce any change in Bmax: 33.7 +/- 3.6 pmol/ml tissue. We hypothetized that methyl-quinuclidinyl-benzylate induced the release of norepinephrine from sympathetic nerve terminals, an effect which could be blocked by guanethidine. Guanethidine alone (10 mg/kg) did not change Bmax: 35.5 +/- 6 pmol/ml tissue. Guanethidine + methyl-quinuclidinyl-benzylate did not induce any significant change in Bmax: 31.5 +/- 5.1 pmol/ml tissue. Therefore, it seems likely that methyl-quinuclidinyl-benzylate acts at the presynaptic level, probably inducing the release of norepinephrine which then causes a down-regulation of beta-adrenoceptors.