Selective affinity of pirenzepine analogues for subtypes of muscarinic receptors

Pirenzepine (PZ), telenzepine (TZ) and quinuclidinyl xanthene-9-carboxylate (QNX) are antimuscarinic agents containing a tricyclic ring system and a basic side chain that have been reported to have selective affinity for the M1 subtype of receptor. They have prepared and examined seven new PZ analogues containing modifications in either the tricyclic ring system, the side-chain, or both. Affinity for M1 type receptors was determined by displacement of specifically-bound [3H]PZ from rat cerebral cortex homogenates. Affinity for M2 type receptors was measured on rat heart homogenate using [3H](-)quinuclidinyl benzilate. The ratio of the K/sub i/'s for M1 and M2 receptors were calculated and compared to PZ. All of the compounds had a higher affinity for M1 than M2 receptors. Three of the compounds were comparable to PZ in selectivity, but the more selective compounds had a weaker affinity for M1 receptors. TZ and QNX were less selective than PZ