The abuse of psychomotor stimulants such as cocaine and methamphetamine is a continuing and very serious problem. In our program to synthesize and evaluate a number of 5-HT agonists and their antagonists, we recently developed a practical nonchromatographic chemical synthesis of the 5-HT2A receptor antagonist MDL100,907 that is providing multigram amounts of this critical research tool. We have also studied the discriminative stimulus effects of MDL100,907 several other 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 studies show that in rats, DOM and MDL100907 discriminative stimulus effects are mediated by 5-HT2A receptors and that ketanserin discriminative stimulus effects involve both 5-HT2A and alpha1 adrenergic receptors. Results in 5-HT depleted rats further suggest that the discriminative stimulus effects of MDL100907 might involve antagonism of endogenous 5-HT and/or inverse agonism at 5-HT2A receptors.

Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2009
Total Cost
$141,477
Indirect Cost
Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
Zip Code
Gilbertson, Scott R; Chen, Ying-Chu; Soto, Claudia A et al. (2018) Synthesis and activity of functionalizable derivatives of the serotonin (5-HT) 5-HT2A receptor (5-HT2AR) antagonist M100907. Bioorg Med Chem Lett 28:1381-1385
Gannon, Brenda M; Galindo, Kayla I; Mesmin, Melson P et al. (2018) Reinforcing Effects of Binary Mixtures of Common Bath Salt Constituents: Studies with 3,4-Methylenedioxypyrovalerone (MDPV), 3,4-Methylenedioxymethcathinone (methylone), and Caffeine in Rats. Neuropsychopharmacology 43:761-769
Gannon, Brenda M; Williamson, Adrian; Rice, Kenner C et al. (2018) Role of monoaminergic systems and ambient temperature in bath salts constituent 3,4-methylenedioxypyrovalerone (MDPV)-elicited hyperthermia and locomotor stimulation in mice. Neuropharmacology 134:13-21
Gannon, Brenda M; Galindo, Kayla I; Mesmin, Melson P et al. (2018) Relative reinforcing effects of second-generation synthetic cathinones: Acquisition of self-administration and fixed ratio dose-response curves in rats. Neuropharmacology 134:28-35
Elmore, Joshua S; Decker, Ann M; Sulima, Agnieszka et al. (2018) Comparative neuropharmacology of N-(2-methoxybenzyl)-2,5-dimethoxyphenethylamine (NBOMe) hallucinogens and their 2C counterparts in male rats. Neuropharmacology 142:240-250
Gannon, Brenda M; Sulima, Agnieszka; Rice, Kenner C et al. (2018) Inhibition of Cocaine and 3,4-Methylenedioxypyrovalerone (MDPV) Self-Administration by Lorcaserin Is Mediated by 5-HT2C Receptors in Rats. J Pharmacol Exp Ther 364:359-366
Perez Diaz, Maylen; Andersen, Monica L; Rice, Kenner C et al. (2017) Effects of a Serotonin 2C Agonist and a 2A Antagonist on Actigraphy-Based Sleep Parameters Disrupted by Methamphetamine Self-Administration in Rhesus Monkeys. Neuropsychopharmacology 42:1531-1538
Pitts, Elizabeth G; Minerva, Adelaide R; Chandler, Erika B et al. (2017) 3,4-Methylenedioxymethamphetamine Increases Affiliative Behaviors in Squirrel Monkeys in a Serotonin 2A Receptor-Dependent Manner. Neuropsychopharmacology 42:1962-1971
Gannon, Brenda M; Galindo, Kayla I; Rice, Kenner C et al. (2017) Individual Differences in the Relative Reinforcing Effects of 3,4-Methylenedioxypyrovalerone under Fixed and Progressive Ratio Schedules of Reinforcement in Rats. J Pharmacol Exp Ther 361:181-189
Lantz, Susan M; Rosas-Hernandez, Hector; Cuevas, Elvis et al. (2017) Monoaminergic toxicity induced by cathinone phthalimide: An in vitro study. Neurosci Lett 655:76-81

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