title: Interaction of orally administered 5-[3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-benzodioxole (MKC-242) with 5-HT1A receptors in rat brain.
abstract: The present study was carried out to clarify whether orally administered 5-{3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy}-1,3-be nzodioxole (MKC-242), a serotonin1A (5-HT1A)-receptor agonist having potent anxiolytic-like and antidepressant-like effects in animal models, binds to 5-HT1A receptors in rat brain. Quantitative autoradiography showed that orally administered MKC-242 (0.1-0.5 mg/kg) caused a significant decrease in 3[H]8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) binding in the hippocampus and dorsal raphe nucleus sections. The decrease in the binding by MKC-242 was observed up to 4 hr after administration, and the effective doses were similar to those in its anxiolytic-like effect in the animal models. Repeated treatment of MKC-242 (0.5 mg/kg/day, p.o.) or buspirone (30 mg/kg/day, p.o.) for 2 weeks did not affect [3H]8-OH-DPAT binding in both sections. These results suggest that orally administered MKC-242 at the low doses that do not show 5-HT1A-receptor-mediated in vivo responses such as the hypothermic effect, adrenocortical effect and the decrease in 5-HT turnover passes the blood-brain barrier and subsequently binds to 5-HT1A receptors in rat brain. In addition, they indicate that repeated stimulation of the receptors by the agonists does not affect the number of the binding sites.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Asano
authors.forename: T
authors.initials: T
authors.lastname: Matsuda
authors.forename: T
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: P
authors.initials: P
authors.lastname: Somboonthum
authors.forename: H
authors.initials: H
authors.lastname: Tasaki
authors.forename: M
authors.initials: M
authors.lastname: Abe
authors.forename: A
authors.initials: A
authors.lastname: Baba
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D004146:Dioxanes / Q000493:pharmacokinetics / Q000494:pharmacology*; D004149:Dioxoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000502:physiology; D018490:Serotonin Agents / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D004146:Dioxanes; D004149:Dioxoles; D011985:Receptors, Serotonin; D018490:Serotonin Agents; D017366:Serotonin Receptor Agonists; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C096294:osemozotan