The abuse of MDMA and other hallucinogenic drugs continues to be a serious problem that is exacerbated by the recent publication of cookbook chemical syntheses and detailed accounts of the doses used and hallucinogenic effects seen in humans for almost all of the 179 phenethylamine and 53 tryptamine analogs that were synthesized and self-administered by A. T. Shulgin and his associates during more than 30 years. These are disturbing developments that substantially aid and encourage clandestine drug production and may presage a resurgence in hallucinogenic drug abuse. We have begun a program to synthesize and evaluate a number of hallucinogenic agents and their antagonists. We recently developed a practical nonchromatographic chemical synthesis of the 5-HT2A receptor antagonist MDL100,907 that is providing this important research tool. We have studied the discriminative stimulus effects of several of these drugs in order to gain further insight into their 5-HT receptor subtype(s) selectivity and the possible receptor role in certain neuropsychiatric disorders. Our results show that the 5-HT2A receptor is involved the stimulus effects of 8-hydroxy DPAT, a protypic 5-HT1A receptor agonist.
