L-365,260

Names

[ Name ]:
L-365,260

[Synonym ]:
L-365,260,N-[(3R)-2,3-Dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl]-N'-(3-methylphenyl)urea
L-365260

Biological Activity

[Description]:

L-365260 is a potent and selective antagonist of non-peptide gastrin and brain cholecystokinin receptor (CCK-B), with Kis of 1.9 nM and 2.0 nM, respectively. L-365260 interacts in a stereoselective and competitive manner with guinea pig stomach gastrin and brain CCK receptors. L-365260 can enhance Morphine analgesia and prevents Morphine tolerance[1][2][3].

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> Cholecystokinin Receptor

Research Areas >> Metabolic Disease

Research Areas >> Neurological Disease

[Target]

Ki: 1.9 nM (gastrin); 2.0 nM (CCK-B)[1]

[In Vitro]

L-365260 (1 μM) strongly attenuates the CCK8S- and CCK4-mediated depolarization in a different neuron[2]. L-365260 exhibits a similar high affinity for brain CCK-B receptors of rats, mice and man, and a lower affinity for gastrin and brain CCK-B (IC50=20-40 nM) receptors in dog tissues[1].

[In Vivo]

L-365260 (0.01-10 mg/kg; s.c.) enhances analgesia induced by a submaximal dose of Morphine (4 mg/kg) in rats[3]. L-365260 (0.2 mg/kg; s.c. twice daily for 5 days) significantly prolongs the duration of Morphine analgesia in rats[3]. L-365260 (0.1-30 mg/kg; p.o.) antagonizes gastrin-stimulated acid secretion in mice (ED50=0.03 mg/kg), rats (ED50=0.9 mg/kg) and guinea pigs (ED50=5.1 mg/kg)[1]. Animal Model: Male Sprague-Dawley rats (300-350 g) were injected with Morphine[3] Dosage: 0.01, 0.05, 0.1, 0.2, 0.75, 1.0, 10.0 mg/kg Administration: S.c. 10 min prior to i.p. injection of 4 mg/kg Morphine Result: Enhanced morphine analgesia.

[References]

[1]. Lotti VJ, et, al. A new potent and selective non-peptide gastrin antagonist and brain cholecystokinin receptor (CCK-B) ligand: L-365,260. Eur J Pharmacol. 1989 Mar 21;162(2):273-80.

[2]. Chung L, et, al. Cholecystokinin action on layer 6b neurons in somatosensory cortex. Brain Res. 2009 Jul 28;1282:10-9.

[3]. Dourish CT, et, al. The selective CCK-B receptor antagonist L-365,260 enhances morphine analgesia and prevents morphine tolerance in the rat. Eur J Pharmacol. 1990 Jan 25;176(1):35-44.

Chemical & Physical Properties

[ Density]:
1.23g/cm3

[ Boiling Point ]:
611.5ºC at 760 mmHg

[ Molecular Formula ]:
C₂₄H₂₂N₄O₂

[ Molecular Weight ]:
398.45700

[ Flash Point ]:
323.6ºC

[ Exact Mass ]:
398.17400

[ PSA ]:
73.80000

[ LogP ]:
3.92110

[ Vapour Pressure ]:
6.85E-15mmHg at 25°C

[ Index of Refraction ]:
1.648

[ Storage condition ]:
2-8°C

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS06, GHS09

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H301-H400

[ Precautionary Statements ]:
P273-P301 + P310

[ RIDADR ]:
UN2811 - class 6.1 - PG 3 - EHS - Toxic solids, organic, n.o.s., HI: all

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