Dual, Postsynaptic 5-HT2B Antagonist and 5-HT1A Agonist Approach to the Treatment of METH/MDMA Addiction and Related Behavioral Disorders
Abstract
The synthesis, in vitro, and preliminary in vivo pharmacology of DDD-024, a novel, pentacyclic compound, is described. It exhibits high affinity to the 5-HT1A and good affinity to the 5-HT2B receptors and is an agonist of the former and antagonist of the latter receptor, a profile which meets with the requirements delineated in our hypothesis proposed in Part 1 (see previous paper). Further, in vivo, it was quite active in METH-seeking behavior test in rats, MDMA-induced hyperlocomotion test in mice, and Porsolt’s forced swim test in rats for antidepressant activity thereby providing definite proof of concept for our hypothesis.
