title: The broad-spectrum antiemetic effects ETI-385 result from stimulation of 5-HT1A and 5-HT1D receptors.
abstract: In the present study, we describe how a nonstoichiometric ratio of the isomers of 8-hydroxy-2-(di-n-propylamino)tetralin (DPAT) produce a broad-spectrum of antiemetic effects in cats and shrews. Determination of the receptor profile of the isomers and testing them separately in cats revealed superior antiemetic effects but severe defensive behavior with the R isomer compared with the S isomer. Differing ratios yielded the best results with the 1:8 (R-S) ratio producing a drug more potent than DPAT and with negligible defensive behavior side effects. Studies with selective 5-HT1D ligands led to the conclusion that this site contributes antiemetic efficacy but is not related to defensive behavior, which is most likely a consequence of 5-HT7 receptor activation. ETI-385 was effective in preventing emetic responses to provocative motion, drugs acting at the chemical trigger zone and cisplatin in both cats and shrews. The results support a clinical trial of this drug for antiemetic effects.
authors.affiliation: Department of Pharmacology, Wright State University, Dayton, OH, USA, james.lucot@wright.edu.
authors.forename: J B
authors.initials: JB
authors.lastname: Lucot
authors.forename: R E L
authors.initials: RE
authors.lastname: Brame
authors.forename: T L
authors.initials: TL
authors.lastname: Garrett
authors.forename: E H
authors.initials: EH
authors.lastname: Pfadenhauer
authors.forename: A
authors.initials: A
authors.lastname: Kumar
authors.forename: D B
authors.initials: DB
authors.lastname: Fick
authors.forename: D R
authors.initials: DR
authors.lastname: Helton
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000932:Antiemetics / Q000494:pharmacology / Q000627:therapeutic use*; D002415:Cats; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007535:Isomerases; D009041:Motion Sickness / Q000188:drug therapy* / Q000209:etiology; D009043:Motor Activity / Q000187:drug effects*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D044346:Receptor, Serotonin, 5-HT1D / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000627:therapeutic use*; D018490:Serotonin Agents / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000932:Antiemetics; D044346:Receptor, Serotonin, 5-HT1D; D058825:Serotonin 5-HT1 Receptor Agonists; D018490:Serotonin Agents; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007535:Isomerases