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

Study Design: Preclinical pharmacology.

Objectives: To determine whether blocking substance P signaling attenuates the hypertension and bradycardia evoked by colorectal distension (CRD) in spinal cord injured (SCI) rats.

Setting: University laboratory in Pennsylvania, U.

Colorectal and bladder prokinetic activity of [Lys, MeLeu, Nle]-NKA after intranasal or sublingual delivery in dogs.

The feasibility of eliciting defecation and urination after intranasal (IN) or sublingual (SL) delivery of a small peptide NK2 receptor agonist, [Lys, MeLeu, Nle]-NKA, was examined using prototype formulations in dogs. In anesthetized animals, administration of 100 or 300 µg/kg IN or 2.0-6.

Potency, efficacy, and selectivity of GR64349 at human recombinant neurokinin NK2 and NK1 receptors.

The affinity, potency, efficacy, and selectivity of the NK2 receptor agonist GR64349 ([Lys,Gly,-R-γ-lactam-Leu]NKA(3-10)) at human recombinant NK2 and NK1 receptors was examined. In radioligand binding studies, GR64349 displaced [I]-NKA binding to NK2 receptors with high affinity (pKi 7.77 + 0.

Prokinetic effects of the neurokinin NK2 receptor agonist [Lys,MeLeu,Nle]-NKA on bladder and colorectal activity in minipigs.

The effects of the neurokinin NK2 receptor agonist [Lys,MeLeu,Nle]-NKA (LMN-NKA) on bladder and colorectal function were examined in minipigs. In anesthetized animals, subcutaneous (SC) administration of 30-100 μg/kg increased peak bladder and colorectal pressures. Increases in bladder and colorectal pressure were inhibited by a 15 min pretreatment with the NK2 receptor antagonist GR 159897 (1 mg/kg intravenously (IV)).

Affinity, potency, efficacy, and selectivity of neurokinin A analogs at human recombinant NK2 and NK1 receptors.

A series of peptide NK2 receptor agonists was evaluated for affinity, potency, efficacy, and selectivity at human recombinant NK2 and NK1 receptors expressed in CHO cells to identify compounds with the greatest separation between NK2 and NK1 receptor agonist activity. Binding studies were performed using displacement of [125I]-NKA binding to NK2 receptors and displacement of [3H]-Septide binding to NK1 receptors expressed in CHO cells. Functional studies examining the increase in intracellular calcium levels and cyclic AMP stimulation were performed using the same cell lines.