Effect of GR205171 on autonomic dysreflexia induced by colorectal distension in spinal cord injured rats.

The effective dose range of GR205171 to alleviate autonomic dysreflexia is consistent with the blockade of NK1 receptors on pelvic sensory afferents in the lumbosacral spinal cord, which may in turn prevent the over-excitation of sympathetic preganglionic neurons (SPNs) that regulate blood pressure and heart rate. The findings provide preclinical support for the utility of NK1 receptor antagonists to treat autonomic dysreflexia in people with SCI. The difference in the effects of the two NK1 receptor antagonists may reflect the ~200-fold lower affinity of CP-99,994 than GR205171 for the rat NK1 receptor.