YM022 [(R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1H-1,4- benzodiazepin-3-yl]-3-(3-methylphenyl)urea]: an irreversible cholecystokinin type-B receptor antagonist.

A functional evaluation of the recently developed cholecystokinin type-B (CCK-B) receptor antagonist YM022 [(R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1H-1,4-++ +benzodiazepin-3-yl]-3-(3-methylphenyl)urea] was undertaken in Chinese hamster ovary cells stably expressing the human CCK-B receptor gene (hCCK-B.CHO). YM022 exhibited high affinity and selectivity for the CCK-B receptor subtype as estimated from [125I]CCK8S displacement studies using membranes derived from hCCK-B.

Pharmacological characterization of a Chinese hamster ovary cell line transfected with the human CCK-B receptor gene.

A stable Chinese hamster ovary cell line expressing the human CCK-B receptor gene is described (hCCK-B.CHO). In radioligand binding experiments employing membranes derived from these cells the rank order of affinity estimated for a series of CCK receptor ligands (CCK-8S > CI988 > PD 135158 > pentagastrin > CCK-8NS > L-365,260 > CCK-4 > LY 288513 > devazepide > A71378 > lorglumide) was found to be in excellent agreement with CCK-B receptor pharmacology described in guinea-pig cortex.

Exposure to high pressure may produce the 5-HT behavioral syndrome in rats.

In addition to the motor events associated with high pressure neurologic syndrome (HPNS), we have observed behavioral changes that resemble the 5-hydroxytryptamine (5-HT) syndrome in free-moving rats exposed to pressures up to 70 ATA. These include a flat body posture, head weaving, reciprocal forepaw treading, and hyperlocomotion. Such changes occur when brain 5-HT levels are raised or when 5-HT receptors are activated.

A comparison of the effects of the selective 5-HT uptake inhibitor WY 27587 on 5-HT uptake into platelets and synaptosomes in the rat.

N-[( 1-[(6-Fluoro-2-naphthalenyl)methyl]- 4-piperidinyl]amino]carbonyl]-3-pyridine carboxamide (Wy 27587), is 320 times more potent as an inhibitor of the uptake of 5-HT than of the uptake of noradrenaline into synaptosomes from the brain of the rat with a Ki against the uptake of 5-HT of 9.2 +/- 1.4 nM.

A kinetic study of the in vitro uptake of [3H]dopamine over a wide range of concentrations by rat striatal preparations.

The uptake of [3H]dopamine was investigated in a number of rat striatal preparations. Kinetic analysis of the rate of uptake by striatal slices indicated that at least two different saturable mechanisms for the catecholamine exist in this region, in addition to a first-order component. One of the uptake mechanisms has a high affinity for [3H]dopamine and the other a low affinity.