Neurology

Rat studies suggest non-catechol-based dopamine D1 receptor agonists could help treat PD more effectively than catechol-based agonists. High throughput screening of about 3 million compounds in an in vitro activity assay identified a non-catechol compound that agonized D1 receptor with an EC₅₀ of 2.519 µM, which was optimized to produce additional non-catechol compounds. In rats, non-catechol agonists had a longer half-life and higher bioavailability than a catechol agonist. In a rat model of PD, a non-catechol agonist increased contralateral rotations in motor tests -- a marker of diminishing response to successive drug doses -- compared with a tool compound catechol-based agonist. Ongoing work by Pfizer Inc. includes clinical testing of undisclosed dopamine D1 receptor agonists that are chemically related to the non-catechol-based agonists...