@article {Hudzik1072, author = {T. J. Hudzik and M. Yanek and T. Porrey and J. Evenden and C. Paronis and M. Mastrangelo and C. Ryan and S. Ross and C. Stenfors}, title = {Behavioral Pharmacology of AR-A000002, a Novel, Selective 5-Hydroxytryptamine1B Antagonist}, volume = {304}, number = {3}, pages = {1072--1084}, year = {2003}, doi = {10.1124/jpet.102.045468}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {The present review summarizes the behavioral pharmacology conducted to profile the anxiolytic and antidepressant potential of the selective 5-hydroxytryptamine (HT)1B antagonist (R)-N-[5-methyl-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydro-2-naphthyl]-4-morpholinobenzamide (AR-A000002). AR-A000002 functions as a 5-HT1B antagonist in vivo, which was shown by the antagonism of the discriminative stimulus effects in the guinea pig of the 5-HT1B agonist 3-(N-methylpyrrolidin-2R-ylmethyl)-5-(3-nitropyrid-2-ylamino)-lH-indole (CP135,807). Anxiolytic activity of AR-A000002 was demonstrated in the separation-induced vocalization paradigm in guinea pig pups, and in a suppressed responding procedure in pigeons and guinea pigs, but only a weak trend was noted in a suppressed responding procedure in squirrel monkeys. Antidepressant efficacy was shown in a number of paradigms. In pigeons and guinea pigs responding under a differential reinforcement of low rates schedule of reinforcement (DRL), AR-A000002 increased the number of reinforcers earned without altering the number of responses made. In guinea pigs trained under a response duration differentiation paradigm, AR-A000002 increased mean lever-press duration. Finally, AR-A000002 was shown to block escape failures in guinea pigs submitted to a learned helplessness paradigm. Taken together, these data suggest utility for 5-HT1B antagonists in the treatment of both anxiety and affective disorders. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/304/3/1072}, eprint = {https://jpet.aspetjournals.org/content/304/3/1072.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }