caa a22 4500 46912184X CHVBK 20180323133141.0 cr unu---uuuuu 170328e19920401xx s 000 0 eng 10.1007/BF02244814 doi (NATIONALLICENCE)springer-10.1007/BF02244814 Quantification of SCH 39166, a novel selective D1 dopamine receptor antagonist, in rat brain and blood [Elektronische Daten] [J. Hietala, T. Seppälä, J. Lappalainen, E. Syvälahti] A gas chromatographic method for measuring concentrations of a novel D1 antagonist SCH 39166 [(−)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5-H-benzo[d]naphto(2,1-6)azepine] in rat brain and plasma was developed. The method was applied to descriptive pharmacokinetics of two subcutaneous doses of SCH 39166 (0.25 mg/kg and 2.5 mg/kg). For comparison, concentrations of the "prototype” D1 antagonist SCH 23390 (0.25 mg/kg, SC) [R-(+)-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1-H-3-benzazepine] were also measured in plasma and brain. SCH 23390 (0.25 mg/kg, SC) had a very short elimination half-life of about 30 min in plasma, and disappeared in a slightly slower manner from striatum and cortex. SCH 39166 (0.25 and 2.5 mg/kg, SC), however, had a longer elimination half-life of about 1.5-2.5 h in plasma and brain. Interestingly, the 2.5 mg/kg dose of SCH 39166 produced only two-to five-fold increases in maximum concentrations in plasma and brain compared to the 0.25 mg/kg dose. The reason for this is not clear. The ability of these two doses of SCH 39166 to induce catalepsy in the bar test was also evaluated. It was found that SCH 39166 in these two doses, unlike SCH 23390, was not cataleptic. In conclusion, these pharmacokinetic features of SCH 39166 in the rat should be useful when designing experiments with this novel selective D1 antagonist. Furthermore, the longer elimination half-life of SCH 39166 makes it a more useful probe in pharmacodynamic comparisons of D1 receptor antagonists and classical as well as atypical neuroleptics. Springer-Verlag, 1992 SCH 23390 nationallicence SCH 39166 nationallicence D1 dopamine receptor nationallicence Antagonist nationallicence Pharmacokinetics nationallicence Rat nationallicence Hietala J. Department of Pharmacology, University of Turku, Kiinamyllynkatu 10, SF-20520, Turku, Finland aut Seppälä T. National Public Health Institute, SF-00300, Helsinki, Finland aut Lappalainen J. Department of Pharmacology, University of Turku, Kiinamyllynkatu 10, SF-20520, Turku, Finland aut Syvälahti E. Department of Pharmacology, University of Turku, Kiinamyllynkatu 10, SF-20520, Turku, Finland aut Psychopharmacology Springer-Verlag 106/4(1992-04-01), 455-458 0033-3158 106:4<455 1992 106 213 https://doi.org/10.1007/BF02244814 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02244814 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hietala J. Department of Pharmacology, University of Turku, Kiinamyllynkatu 10, SF-20520, Turku, Finland aut NATIONALLICENCE 700 1- Seppälä T. National Public Health Institute, SF-00300, Helsinki, Finland aut NATIONALLICENCE 700 1- Lappalainen J. Department of Pharmacology, University of Turku, Kiinamyllynkatu 10, SF-20520, Turku, Finland aut NATIONALLICENCE 700 1- Syvälahti E. Department of Pharmacology, University of Turku, Kiinamyllynkatu 10, SF-20520, Turku, Finland aut NATIONALLICENCE 773 0- Psychopharmacology Springer-Verlag 106/4(1992-04-01), 455-458 0033-3158 106:4<455 1992 106 213 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer