Disease relevance of GR64349

• Each agonist caused bradycardia, but GR64349 was most effective (34 +/- 4% decrease in heart rate with 32 nmol, n = 8) [1].

Psychiatry related information on GR64349

• In photocell cages, the NK-2-agonist, GR64349, and the NK-3 agonist, senktide, both increased motor activity in a dose-dependent manner [2].

High impact information on GR64349

• The design and synthesis of potent and selective neurokinin NK-2 receptor agonists 12 (GR64349) and 31 are described, together with structure-activity relationships for related analogues [3].
• Intradermal injections of the NK1 receptor agonist GR73632 produced dose-dependent scratching, while the NK2 agonist GR64349 and the NK3 agonist senktide were without effects [4].
• 5. Background activity was significantly enhanced by GR73632, GR64349, SP and NKA but not by senktide or NKB [5].
• By contrast, the selective NK-2 and NK-3 receptor agonists, GR64349 and [MePhe7]NKB, produced concentration-dependent pressor responses and were more potent than SP (116 +/- 8 and 134 +/- 15 mm Hg increases in PP at 33.3 nmol, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)[6]
• In vivo, in the anaesthetised guinea-pig, GR159897 (0.12 mg.kg-1 i.v.) potently antagonised bronchoconstriction induced by GR64349 (dose-ratio = 28), with a long duration of action (3 h) [7].

Gene context of GR64349

• However, only the NK-2 receptor agonist, GR64349, inhibited drinking without producing other behavioural effects [8].
• GR73632 (0.1 and 0.3 nmol/kg) and GR64349 (0.3 nmol/kg), but not h.alpha CGRP (0.01-0.3 nmol/kg) or substance P(0.01-1.0 nmol/kg), then produced a more prolonged increase in CBF, the peak effect occurring 10-15 min after injection [9].
• In contrast, in RbT, only NKA and the selective NK2-receptor agonist, GR64349 were potent, indicating the presence of NK2-receptors [10].
• However, in GPT both NK1- and NK2-receptors appear to mediate contraction to NKs since NKA, GR73632 and GR64349 were highly potent and SP and SPOMe moderately potent agonists [10].

Analytical, diagnostic and therapeutic context of GR64349

• Prominent increases in ventricular contractility and perfusion pressure also occurred with 32 nmol of GR64349 (25 +/- 6 and 33 +/- 4%, respectively). ¿Sar(9), Met(O(2))(11)SP was unique in having a high potency for decreasing ventricular contractility and perfusion pressure [1].

References