RESUMO
Pierre Fabre is developing donitriptan, a piperazide 5-HT1D agonist, as a potential treatment for migraine [175854]. In January 2001, donitriptan had completed phase I trials for migraine and was scheduled to enter phase II development [396027]. This compound has an increased potency and, importantly, markedly higher intrinsic activity in comparison to the well described tryptamine derivatives, naratriptan, zolmitriptan and sumatriptan [295769].
Assuntos
Drogas em Investigação , Nitrilas/farmacologia , Piperazinas/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Animais , Ensaios Clínicos Fase I como Assunto , Avaliação Pré-Clínica de Medicamentos , Humanos , Transtornos de Enxaqueca/tratamento farmacológico , Estrutura Molecular , Nitrilas/química , Nitrilas/uso terapêutico , Nitrilas/toxicidade , Piperazinas/química , Piperazinas/uso terapêutico , Piperazinas/toxicidade , Agonistas do Receptor de Serotonina/química , Agonistas do Receptor de Serotonina/uso terapêutico , TriptaminasRESUMO
The phenylisopropylamine PMMA or N-methyl-1-(4-methoxyphenyl)-2-aminopropane, a structural hybrid of paramethoxyamphetamine (PMA) and methamphetamine, has been previously shown to unexpectedly lack amphetamine-like or hallucinogen-like stimulus properties in animals. For example, in tests of stimulus generalization, neither a (+)amphetamine stimulus nor a DOM stimulus generalized to PMMA. It has also been shown, however, that stimulus generalization does occur in animals trained to discriminate the designer drug MDMA ("Ecstasy" or N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane) from vehicle. In order to further characterize this unique agent, we trained a group of six Sprague-Dawley rats to discriminate 1.25 mg/kg of PMMA (ED50 = 0.44 mg/kg) from saline vehicle. The PMMA stimulus failed to generalize to the phenylisopropylamine stimulant (+)amphetamine, or to the phenylisopropylamine hallucinogen DOM. Stimulus generalization occurred to (+/-)MDMA (ED50 = 1.32 mg/kg) and S(+)MDMA (ED50 = 0.48 mg/kg). Partial generalization occurred with R(+)MDMA, PMA, 3.4-DMA, and fenfluramine. The PMMA stimulus also generalized to the alpha-ethyl homolog of PMMA (EH/PMMA, ED50 = 1.29 mg/kg). Taken together, the results of these studies suggest that PMMA is an MDMA-like agent that lacks the amphetamine-like stimulant character of MDMA. These findings support our previous suggestion that PMMA be considered the structural parent of the MDMA-like family of designer drugs.
Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Drogas Desenhadas/farmacologia , Aprendizagem por Discriminação/efeitos dos fármacos , Generalização do Estímulo , Metanfetamina/análogos & derivados , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Animais , Avaliação Pré-Clínica de Medicamentos , Masculino , Metanfetamina/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
Ten cyclic animals (1-10), including a form of decahydro-5H-pyrido [1',2';5,1] imidazo [3,4-a]-beta-carboline, were obtained by treating erythro 1-(2'-piperidyl)-1,2,3,4-tetrahydro-beta-carboline with aldehydes. The anticonvulsant action of those compounds (1-10) was investigated in mice using a behavioral test. Only 5-(3-chlorophenyl) (2) and 5-(3-pyridyl) (9) derivatives showed an anticonvulsant activity in the electric seizure test, but their therapeutic index was inferior to that of phenytoin.