Muscarinic receptor subtype specificity of 5'-(isobutylthio)-adenosine (SIBA) and its analogs

1. 5'(Isobutylthio)-adenosine (SIBA) and its analogs, at 100 microM, inhibited [3H]N-methyl-scopolamine binding to homogenates of whole brain and cortex (mainly M1 subtype receptors) by 11-30% and to cerebellum (mainly M2 subtype receptors) by 20-39%. 2. At 0.01-1.0 microM, stimulation of [3H]QNB and NMS-inaccessible [3H]QNB binding was observed, with the most induced by 1 microM 3-deaza-SIBA. 3. In contrast, [3H]pirenzepine ([3H]PZ) binding to whole brain and cortex was inhibited in a dose-dependent manner with Ki values in the microM range. 4. As antagonists of acetylcholine-induced contraction of guinea pig ileum (mainly M2 subtype receptors), the analogs were slightly more potent than pirenzepine, but several orders of magnitude less than atropine; the order of potency was opposite that determined for the binding of [3H]PZ to cortex. 5. Thus, SIBA and its analogs may have differential effects on muscarinic receptor subtypes and show some specificity for the M1 receptor subtype.