Disease relevance of L 733060

• CONCLUSIONS: The findings demonstrate that substance P is a mitogen and also indicate that the neurokinin-1 receptor antagonist L-733,060 acts on both human retinoblastoma cell lines as an antitumoral agent [1].
• We tested the effects of the selective NK-1 receptor antagonists WIN-51,708 and L-733,060 on several markers of dopaminergic terminal toxicity in the mouse striatum [2].
• The versatility of the method is illustrated by the asymmetric syntheses of neurokinin substance P receptor antagonist L-733,061 (ent-1), (-)-deoxocassine (4), and an inhibitor of HIV proteases (5a) [3].
• Thus, this study demonstrates that substance P acts as a mitogen in the SKN-BE(2) neuroblastoma and GAMG glioma cell lines, and that the antitumoural action of L-733,060 on both human cell lines occurs through the NK1 receptor [4].
• Antitumoural action of L-733,060 on neuroblastoma and glioma cell lines [5].

High impact information on L 733060

• RESULTS: Nanomolar concentrations of substance P increased the growth of both cell lines and micromolar concentrations of L-733,060 inhibited the growth of the two cell lines studied, with and without previous administration of substance P [1].
• Enantioselective inhibition of the formalin paw late phase by the NK1 receptor antagonist L-733,060 in gerbils [6].
• In contrast, the non-brain penetrant quaternary ketone NK1 receptor antagonist, L-743,310 (3 mg/kg), did not attenuate the response to formalin, indicating that the antinociceptive effect of blockade of NK1 receptors by L-733,060 in this assay is centrally-mediated [6].
• Also, pretreatment with the specific NK-1 receptor antagonist (2S,3S)-3-([3,5-bis[trifluoromethyl)phenyl]methoxy)-2-phenylpiperidine (L-733,060) significantly inhibited the inflammatory effects of both toxin A and anandamide [7].
• In guinea-pigs, i.c.v. infusion of the selective substance P agonist GR73632 (0.1 nmol) elicited a pronounced vocalisation response that was blocked enantioselectively by the NK(1) receptor antagonists CP-99,994 and L-733,060 (0.1-10 mg/kg) [8].

Biological context of L 733060

• This study investigated for the first time acute effects of SP and the neurokinin-1 (NK-1) receptor antagonist L-733060 on long term potentiation (LTP) in the hippocampus [9].

Anatomical context of L 733060

• L-733,060 inhibited the growth of the WERI-Rb-1 and Y-79 cell lines in a dose-dependent manner [1].
• We found that the specific human NK-1-RA L-733060, in contrast to the SSRI fluvoxamine (IC50=10(-7.96)M) did not inhibit 5-HT uptake in human brain synaptosomes and did not modulate fluvoxamine-induced 5-HT uptake inhibition at 1 muM [10].

Associations of L 733060 with other chemical compounds

• Similarly, vocalisations in guinea-pig pups separated from their mothers were blocked enantioselectively by the highly brain-penetrant NK(1) receptor antagonists L-733,060 and GR205171 (ID(50) 3 mg/kg), but not by the poorly brain-penetrant compounds LY303870 and CGP49823 (30 mg/kg) [8].
• In separate experiments two different neurokinin-1 (NK-1) receptor antagonists (D-Arg(1), D-Pro(2), D-Trp(7,9), Leu(11), or L-733,060) were perfused via the microdialysis probe for one hour in awake and freely moving animals that were subsequently injected i.p. with cocaine [11].
• In a separate experiment, infusion through the microdialysis probe of the neurokinin-1 receptor antagonist L-733,060 significantly decreased cocaine-evoked striatal dopamine overflow (approximately 50% inhibition at 30 minutes after cocaine administration) [12].
• This loss was prevented by preexposure (30 min before the first injection of methamphetamine) of the neurokinin-1 receptor antagonist L-733,060 [13].
• Furthermore, oral administration of the NK1 antagonists MK-869 (10 mg/kg), L-742694 (10 mg/kg), L-733060 (10 mg/kg), CP-99994 (30 mg/kg), and CP-122721 (3-30 mg/kg) reduced immobility time [14].

Gene context of L 733060

• We infused the neurokinin-1 receptor (NK-1R) antagonist, L-733,060, into the striatum of freely moving rats via a microdialysis probe in order to assess the effects of SP on cocaine-induced DA overflow in the striatum [15].
• L-733,060, a novel tachykinin NK1 receptor antagonist; effects in [Ca2+]i mobilisation, cardiovascular and dural extravasation assays [16].
• The SP-specific NK-1 receptor antagonist L-733060 did not influence fEPSP in a concentration of 1 microM [9].

References