Determination of brain concentrations of 8-hydroxy-2-(di-n-propylamino)tetralin by liquid chromatography with electrochemical detection.
A liquid chromatographic method using electrochemical detection is described for the assay of brain concentrations of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), centrally acting serotonin agonists selective for the 5HT-1A subtype of serotonin receptors. The method is sensitive to approximately 5 ng/g concentrations. After a 1mg/kg s.c. dose of 8-OH-DPAT in rats, its concentration in whole brain declined rapidly during the first 4 hr with a half-life of 26 min. At 30 min after a 1 mg/kg s.c. dose of 8-OH-DPAT, concentrations were approximately equal in hypothalamus, striatum, hippocampus, cerebellum and brain stem but were slightly lower in midbrain. 8-OH-DPAT disappeared from hypothalamus, midbrain and hippocampus at similar rates during the first 90 min after a 1 mg/kg s.c dose. Concentrations of 8-OH-DPAT in whole brain were markedly higher after s.c. than after i.p. administration of 8-OH-DPAT, consistent with earlier data showing 8-OH-DPAT to be more potent when given s.c. than when given i.p. in decreasing brain concentrations of 5-hydroxyindoleacetic acid. Pretreatment with proadifen (SKF-525A), an inhibitor of microsomal drug metabolism, slightly increased brain concentrations of 8-OH-DPAT. Pindolol, which antagonized the elevation of serum corticosterone concentration by 8-OH-DPAT, did not alter brain concentrations of 8-OH-DPAT. The analytical method should be useful in correlating brain concentrations of 8-OH-DPAT with various neurochemical, behavioral or other functional effects that have been described for this compound.
Perry
K W
KW
Lilly Research Laboratories, Eli Lilly & Co., Indianapolis, IN 46285.
Fuller
R W
RW
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001923:Brain Chemistry; D002853:Chromatography, Liquid; D008297:Male; D009281:Naphthalenes / Q000032:analysis*; D010869:Pindolol / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000032:analysis*
D009281:Naphthalenes; D011725:Pyridines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C013109:metapyrone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010869:Pindolol