RESUMO
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.
Assuntos
Antieméticos/uso terapêutico , Enjoo devido ao Movimento/tratamento farmacológico , Atividade Motora/efeitos dos fármacos , Receptor 5-HT1A de Serotonina/metabolismo , Receptor 5-HT1D de Serotonina/metabolismo , Agonistas do Receptor 5-HT1 de Serotonina/uso terapêutico , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , 8-Hidroxi-2-(di-n-propilamino)tetralina/uso terapêutico , Animais , Antieméticos/farmacologia , Gatos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Isomerases , Enjoo devido ao Movimento/etiologia , Serotoninérgicos/farmacologia , Serotoninérgicos/uso terapêuticoRESUMO
The law of toxic substances dates back to Medieval England, but the present comprehensive federal regulatory scheme was developed over the past two decades. This article presents a brief overview of the federal law of air and water pollution, solid waste control, and the regulation of chemicals.
