Jonathan Laird Gross

5-HT(2C) agonists as therapeutics for the treatment of schizophrenia.

The 5-HT(2C) receptor is a highly complex, highly regulated receptor which is widely distributed throughout the brain. The 5-HT(2C) receptor couples to multiple signal transduction pathways leading to engagement of a number of intracellular signaling molecules. Moreover, there are multiple allelic variants of the 5-HT(2C) receptor and the receptor is subject to RNA editing in the coding regions. The complexity of this receptor is further emphasized by the studies suggesting the utility of either agonists or antagonists in the treatment of schizophrenia. While several 5-HT(2C) agonists have demonstrated clinical efficacy in obesity (lorcaserin, PRX-000933), the focus of this review is on the therapeutic potential of 5-HT(2C) agonists in schizophrenia. To this end, the preclinical profile of 5-HT(2C) agonists from a neurochemical, electrophysiological, and a behavioral perspective is indicative of antipsychotic-like efficacy without extrapyramidal symptoms or weight gain. Recently, the selective 5-HT(2C) agonist vabicaserin demonstrated clinical efficacy in a Phase II trial in schizophrenia patients without weight gain and with low EPS liability. These data are highly encouraging and suggest that 5-HT(2C) agonists are potential therapeutics for the treatment of psychiatric disorders.

The synthesis and identification of 4,6-diaminoquinoline derivatives as potent immunostimulants

Abstract The synthesis of a number of 4,6-diaminoquinoline derivatives is described as well as their evaluation in a mouse protection model designed to identify immunostimulant activity. These compounds represent a novel series of potent immunostimulants.

Investigation of side-chain sar, formulation and injection site toleration of pyrazolo[3,4-f]quinoline derivatives: a potent series of in vivo active immunostimulants

Abstract Pyrazolo[3,4-f]quinoline derivatives represent a novel class of immunostimulant with potent in vivo effects in amurine infection model. Side-chain SAR, formulation issues and injection site toleration studies have been addressed and compounds suitable for extensive in vivo evaluation have been identified. The results of these investigations are presented in this report.