Disease relevance of L-659877

• Epinastine could not block bronchospasm in the presence of 1 mg/kg NK2 receptor antagonist L 659877 or 20 microg/kg potassium channel blocker iberiotoxin, suggesting the epinastine was acting on a neurokinin- and potassium channel-mediated mechanism [1].

High impact information on L-659877

• An increase in NO levels induced by SP was inhibited by L-NAME and the NK(1) tachykinin receptor antagonist L-668,169, but not by the NK(2) tachykinin receptor antagonist L-659,877 [2].
• SP-induced scratching was inhibited by the NK1 receptor antagonists spantide and L-668,169, but not by the NK2 antagonist L-659,877 [3].
• The present study was undertaken to assess the activity of the neurokinin-2 (NK2) tachykinin receptor-selective antagonists MEN 10,376, L 659,877 and R 396 along with the NK2 receptor-selective ligand, MDL 28,564 on the isolated guinea pig gallbladder [4].
• 1. The effect of newly developed, receptor-selective tachykinin antagonists (GR 71,251 for NK1 receptors, MEN 10,376 and L 659,877 for NK2 receptors) on noncholinergic transmission to the circular muscle of the guinea-pig ileum has been investigated [5].
• 5. For L-659,877 and R396, comparison was made between activity in guinea-pig trachea and in preparations known to contain tachykinin receptors predominantly of the NK2 type [6].

Biological context of L-659877

• The NK2 receptor antagonists L-659,877 and GR 159897 (1 nmol/l) strongly inhibited this arteriolar vasodilation [7].

Anatomical context of L-659877

• In the rabbit trachea, both L-659,877 and R396 had effects similar to those in guinea-pig trachea [6].
• In contrast, in the rat colon muscularis mucosae, both L-659,877 and R396 appeared to behave competitively with pKB values against GR64349 of 7.83 and 6.90 respectively [6].
• It is also substantially reduced by combined vagotomy and atropinization or by pretreatment with the NK2 receptor antagonist L-659,877, suggesting involvement of neuropeptide-mediated neural pathways [8].
• The activity of SR 48,968, a novel non-peptide antagonist of tachykinin NK2 receptors was evaluated in vitro in several bioassays for the NK2 receptor (rabbit pulmonary artery, rabbit bronchus, hamster trachea, rat vas deferens) and compared to that of the peptide antagonists, MEN 10,376, L 659,877 and MDL 29,913 [9].
• In contrast, the rank order of displacement of [125I]neurokinin A-specific binding to hamster bladder membranes was: L-659,877 > R 396 > MEN 10,376 > MEN 10,207 [10].

Associations of L-659877 with other chemical compounds

• However, pretreatment with a peripheral NK-2-selective antagonists, L-659,877, attenuated the SP-induced responses but not the NKA-induced responses [11].
• This response was blocked by concurrent intranigral administration of the NK-1 tachykinin receptor antagonist RP 67580 (2 nmol), but not by NK-2 (L-659,877) or NK-3 ([Trp7, beta-Ala8]NKA4-10) antagonists [12].
• The NK2-selective antagonist L-659,877, at a dose of 10(-6) M, abolished the effect of SP (10(-8) M) without affecting basal phosphoinositide breakdown [13].
• Evidence for activation of tachykinin NK1 and NK2 receptors by scyliorhinin I was obtained by using the selective tachykinin antagonists FK 888, MEN 10,376 and L 659,877 [14].
• 3. The inhibitory effect on drinking observed after central injection of the NK-2 agonist, GR64349, was attenuated by co-administration of the NK-2 antagonist, L-659,877, but not by the NK-1 antagonist, GR82334 [15].

Gene context of L-659877

• On the contrary, the NK-2 receptor antagonist L 659,877 (0.1-1 mumol/kg i.v.) abolished the effect of [beta Ala8] NK-A(4-10) (1 nmol/kg i.v.), but failed to affect the response to [Sar9]SP sulfone [16].
• The NK2 receptor selective antagonist L-659,877 (cyclo[Leu-Met-Gln-Trp-Phe-Gly]) inhibited the stimulation of PI turnover and bladder contractions induced by all three tachykinins [17].
• 4. Spantide (3 microM) selectively antagonized the SP-induced contraction while L-659,877 (3-10 microM) or MEN 10,376 (10-30 microM) which are NK2 receptor selective antagonists selectively blocked the response to NKA [18].
• The non-selective NK receptor antagonist spantide I only slightly reduced the contractile response to NP gamma, as did the selective NK1 antagonist GR 82,334, and the selective NK2 antagonist L-659,877 and MEN 10,376 [19].

Analytical, diagnostic and therapeutic context of L-659877

• The antagonists MEN 10,207 and L 659,877 inhibited the noncholinergic contraction to electrical stimulation in a concentration-dependent manner; L 668,169 and R 396 were poorly effective [20].

References