Development of a presynaptic 5-HT1A antagonist.
A new 5-HT(1A) silent antagonist 14 (5-HT(1A) IC(50)=2.2 nM) antagonizes the effects of agonists on reciprocal forepaw treading behavior, on neuronal firing in the rat dorsal raphé, and on 5-HT(1A) release in the raphé and hippocampus. While 14 alone was inactive in the social interaction paradigm, it completely reversed the social interaction activity of the serotonergic compounds (buspirone, 1, and 2).
Mattson
Ronald J
RJ
Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492-7660, USA. mattsonr@bms.com
Catt
John D
JD
Sloan
Charles P
CP
Gao
Qi
Q
Carter
Richard B
RB
Gentile
Anthony
A
Mahle
Cathy D
CD
Matos
F Fatima
FF
McGovern
Rachel
R
VanderMaelen
Cam P
CP
Yocca
Frank D
FD
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D002065:Buspirone / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D007398:Interpersonal Relations; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017661:Receptors, Presynaptic / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000138:chemical synthesis*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013329:Structure-Activity Relationship
D014151:Anti-Anxiety Agents; D017661:Receptors, Presynaptic; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002065:Buspirone