RESUMO
Several cytisine derivatives have been developed in the search for more selective drugs at nicotinic acetylcholine receptors (nAChR). Binding experiments in transfected cell lines showed that the iodination of cytisine in the position 3 of the pyridone ring increased potency at alpha7-nAChR and to a lesser extent at the alpha4beta2 subtypes, both of which are widely expressed in the brain. However, no in vivo studies have been published on this compound. Inhibition curves presented here using wild type, beta2, and beta4-null mutant mice confirm that 3-IC binds to alpha4beta2 *, alpha7 * and alpha3beta4 * receptors with higher affinity than cytisine (asterisk indicates the receptor may contain additional subunits, Lukas et al., 1999). Intraperitoneal injection of 3-iodocytisine (3-IC) induced considerable dose-dependent hypothermia in DBA/2J and C57BL/6J mice. This response was blocked by mecamylamine and partially inhibited by hexamethonium. beta4-null mice displayed significantly less 3-IC-induced hypothermia than wild-type mice, beta2-null mice were somewhat less affected than wild types, while responses of alpha7 *-null mice were similar to wild types. Mice treated chronically with 3-IC display a marked increase in alpha7 * and alpha4beta2 * binding sites determined by radioligand binding in membrane preparations from cerebral cortex and hippocampus. Quantitative autoradiographic analysis of 28 brain regions of mice treated with 3-IC was consistent with the membrane binding, detecting an increase of cytisine-sensitive [(125)I]epibatidine binding sites, while cytisine-resistant [(125)I]epibatidine sites were unchanged. [(125)I]alpha-Bungarotoxin binding sites also exhibited up-regulation. These results give a first evaluation of in vivo consequences of 3-IC as a potent agonist with marked effects on mice.
Assuntos
Alcaloides/farmacologia , Azocinas/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Hipotermia/induzido quimicamente , Quinolizinas/farmacologia , Receptores Nicotínicos/metabolismo , Animais , Sítios de Ligação , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Relação Dose-Resposta a Droga , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipotermia/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Camundongos Knockout , Distribuição Aleatória , Receptores Nicotínicos/genética , Receptor Nicotínico de Acetilcolina alfa7RESUMO
Two hundred and three (203) open heart surgical procedures have been performed at the Complejo Hospitalario Metropolitano, from January 1997 to august 1998; Hundred and twenty-three (123) were of myocardial revascularization and twenty-four (24) of these patients were selected for revascularization without the assistance of the extracorporeal circulation machine. They were patients with chronic stable angina and had lesions of more than 95% in the descending anterior artery, high ventriculo-lateral branch and right coronary artery up to the crux cordis. In nineteen (19) patients the surgical approach was though a medical sternotomy; in four (4) through a left anterolateral thoracostomy and in three (3) of these patients a transverse sternotomy was added. There were no deaths perioperatively and at thirty (30) days there were no evidences of new Q waves or residual angina. With this technique, the time in the Intensive Care Unit and in the hospital has diminished; the patients also required less time in mechanical ventilation; less vasoactive amines are needed. In the operating room less equipment is necessary and the costs are significantly lower.