RESUMO
Tecostanine (1) was isolated from Tecoma stans leaves. Its sterochemistry was elucidated as well as its antihyperglycemic activity and its affinity to opioid and nicotinic receptors. The oxalate salt of 1 did not significantly affect blood glucose levels in normoglycaemic and hyperglycaemic rats. It did not appear to interact with opioid receptors (mu type) and showed only moderate affinity to the nicotinic receptor.
Assuntos
Alcaloides/química , Alcaloides/farmacologia , Bignoniaceae/química , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Plantas Medicinais/química , Terpenos/química , Terpenos/farmacologia , Animais , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Masculino , México , Modelos Moleculares , Conformação Molecular , Ratos , Ratos Sprague-Dawley , Receptores Nicotínicos/efeitos dos fármacos , Receptores Opioides/efeitos dos fármacosRESUMO
Ambasilide, a representative of Class III antiarrhythmics, was reported to prolong the cardiac action potential duration in the dog, with little or no effect on Ca and Na currents. We synthesised a series of ambasilide analogues, having the 3,8-diazabicyclo-[3.2.1]-octane moiety instead of the 3,7-diazabicyclo-[3.3.1]-nonane present in ambasilide. The compounds were tested both in vitro extracellular electrophysiological assays and by the conventional microelectrode technique. Most of them lengthened the effective refractory period (ERP) with no change or slight increase on the impulse conduction time (ICT). Similarly some of the tested compounds lengthened the action potential duration (APD), a typical Class III feature, without exerting any significant effect on the maximal rate of depolarization, therefore apparently lacking Class I antiarrhythmic activity.
Assuntos
Aminobenzoatos/química , Aminobenzoatos/farmacologia , Antiarrítmicos/química , Antiarrítmicos/síntese química , Antiarrítmicos/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/química , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Ventrículos do Coração/efeitos dos fármacos , Aminobenzoatos/síntese química , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Cães , Desenho de Fármacos , Técnicas Eletrofisiológicas Cardíacas , Feminino , Técnicas In Vitro , Masculino , Microeletrodos , Modelos Moleculares , Conformação Molecular , Relação Estrutura-AtividadeRESUMO
A series of N,N-disubstituted-2-methylpiperazines (3a-e) has been synthesized and compounds tested both in vitro and in vivo for their analgesic properties. Binding studies showed that the new compounds are devoid of relevant affinity towards mu receptors. However, compound 3a displayed significant analgesic properties both in the hot plate test and in the mouse phenyl-p-benzoquinone induced abdominal constriction test (MAC), whereas the other derivatives were found active only in MAC test. Moreover, it should be noted that compound 3a elicited a Straub-tail reaction also at the lowest administered dose (10 mg/kg, ip) and this effect was antagonized by naloxone.