Effect of 5-[3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-benzodioxole HCl (MKC-242), a novel 5-HT1A-receptor agonist, on aggressive behavior and marble burying behavior in mice.
Behavioral effects of 5-[3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-be nzodioxole HCl (MKC-242), a novel 5-HT1A-receptor agonist, were evaluated using animal models of anxiety and obsessive compulsive disorder and compared against reference compounds. MKC-242 suppressed foot shock-induced fighting behavior without loss of motor coordination in mice as the reference compounds did. The ED50 values of MKC-242, buspirone, tandospirone and diazepam were 1.7, 42, 80 and 2.0 mg/kg, p.o., respectively. The duration of the suppression of fighting by MKC-242 was longer than those of buspirone and tandospirone and comparable to that of diazepam. Similar results were also obtained with the water-lick conflict test in rats. The plasma concentration of MKC-242 in rats was much higher than the reported value of buspirone during 0.25-6 hr after oral administration. In addition, MKC-242 reduced marble burying behavior without reduction of motor activity. Fluoxetine, tandospirone and diazepam also reduced the behavior at non-sedative doses. These findings indicate that MKC-242 possesses a longer-lasting anxiolytic effect than azapirones. This might be due to the high concentration of the compound in plasma. In addition, it is also suggested that MKC-242 possesses an antiobsessional effect.
Abe
M
M
Pharmaceuticals Laboratory I, Yokohama Research Center, Mitsubishi Chemical Corporation, Japan.
Nakai
H
H
Tabata
R
R
Saito
K
K
Egawa
M
M
D000374:Aggression / Q000187:drug effects*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy; D002065:Buspirone / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004146:Dioxanes / Q000097:blood / Q000494:pharmacology*; D004149:Dioxoles / Q000097:blood / Q000494:pharmacology*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D054833:Isoindoles; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009770:Obsessive Behavior / Q000188:drug therapy*; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D004146:Dioxanes; D004149:Dioxoles; D054833:Isoindoles; D010879:Piperazines; D011743:Pyrimidines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; C055267:tandospirone; C096294:osemozotan; D003975:Diazepam; D002065:Buspirone