RESUMEN
The authors report two patients with isolated unilateral tongue atrophy. Magnetic resonance imaging (MRI) of the brain stem and angio-MRI demonstrated a dolichovertebral artery with an abnormal course compressing the medulla oblongata at the emergence of the hypoglossal rootlets. The semeiological observation of a sectorial and not uniform distribution of atrophy in the half-affected tongue is discussed in relation to the lesional site.
Asunto(s)
Nervio Hipogloso/patología , Síndromes de Compresión Nerviosa/etiología , Arteria Vertebral/anomalías , Anciano , Circulación Cerebrovascular , Humanos , Nervio Hipogloso/fisiopatología , Imagen por Resonancia Magnética , Masculino , Bulbo Raquídeo/patología , Bulbo Raquídeo/fisiopatología , Persona de Mediana Edad , Atrofia Muscular/etiología , Atrofia Muscular/patología , Atrofia Muscular/fisiopatología , Síndromes de Compresión Nerviosa/patología , Síndromes de Compresión Nerviosa/fisiopatología , Lengua/patología , Lengua/fisiopatología , Arteria Vertebral/patologíaRESUMEN
We have identified GR138950, a potent antagonist of the angiotensin II receptor with high oral bioavailability, as our second drug candidate to GR117289. Using GR117289, a compound with moderate bioavailability (20%) in man as a lead, we pursued a strategy aimed at enhancing bioavailability. The strategy was based on SAR established around the diacid GR117289, and from this, it was proposed that a monoacid, in particular a trifluoromethanesulfonamide, should be better absorbed after oral administration and have enhanced oral bioavailability. This led to the identification of GR138950, a potent antihypertensive agent in the renal hypertensive rat, causing sustained falls in blood pressure after oral administration. Oral bioavailability of GR138950 in rats and dogs is high, confirming that GR138950 is well absorbed after oral administration. Moreover, the low plasma clearance and long plasma half-life suggest that this compound will be suitable for once a day administration. Furthermore, the preliminary data indicate that the high bioavailability of GR138950 seen in rats and dogs translates to man. These results demonstrate clearly that GR138950 has the potential to be a clinically effective antihypertensive agent. Further studies are in progress to evaluate GR138950 in the treatment of hypertension.