PT - JOURNAL ARTICLE AU - T. J. Hudzik AU - M. Yanek AU - T. Porrey AU - J. Evenden AU - C. Paronis AU - M. Mastrangelo AU - C. Ryan AU - S. Ross AU - C. Stenfors TI - Behavioral Pharmacology of AR-A000002, a Novel, Selective 5-Hydroxytryptamine<sub>1B</sub> Antagonist AID - 10.1124/jpet.102.045468 DP - 2003 Mar 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 1072--1084 VI - 304 IP - 3 4099 - http://jpet.aspetjournals.org/content/304/3/1072.short 4100 - http://jpet.aspetjournals.org/content/304/3/1072.full SO - J Pharmacol Exp Ther2003 Mar 01; 304 AB - 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