(R)-(+)-HA-966

[Description]:

(R)-(+)-HA-966 ((+)-HA-966) is a partial agonist/antagonist of glycine site of the N-methyl-D-aspartate (NMDA) receptor complex. (R)-(+)-HA-966 selectively blocks the activation of the mesolimbic dopamine system by amphetamine[1][2]. (R)-(+)-HA-966 can cross the blood-brain barrier and has the potential for neuropathic and acute pain[3].

[Related Catalog]:

Signaling Pathways >> Neuronal Signaling >> iGluR

Research Areas >> Neurological Disease

Signaling Pathways >> Membrane Transporter/Ion Channel >> iGluR

[Target]

glycine site of the NMDA receptor[1][2]

[In Vivo]

(R)-(+)-HA-966 ((+)-HA-966; 10 mg/kg; IV) significantly attenuates the dose-dependent pressor response and the associated tachycardic response elicited by systemic NMDA (125, 250, 500, and 1000 mg/kg; i.v.)[3]. (+)-HA-966 (30, 100 mg/kg; IP) dose-dependently blocks the enhancement of dopamine synthesis induced in the nucleus accumbens by amphetamine, but is without effect on the increase in dopamine synthesis in the striatum in male BKTO mice (20-30g)[1]. Animal Model: Sprague-Dawley rats (11 to 12 weeks old)[3] Dosage: 10 mg/kg Administration: IV Result: Significantly attenuated the dose-dependent pressor response and the associated tachycardic response elicited by systemic NMDA.

[References]

[1]. Hutson PH, et al. R-(+)-HA-966, a glycine/NMDA receptor antagonist, selectively blocks the activation of the mesolimbic dopamine system by amphetamine. Br J Pharmacol. 1991 Aug;103(4):2037-44.

[2]. Witkin JM, et al. Discriminative stimulus effects of R-(+)-3-amino-1-hydroxypyrrolid-2-one, [(+)-HA-966], a partial agonist of the strychnine-insensitive modulatory site of the N-methyl-D-aspartate receptor. J Pharmacol Exp Ther. 1995 Dec;275(3):1267-73.

[3]. Christensen D, et al. The antinociceptive effect of combined systemic administration of morphine and the glycine/NMDA receptor antagonist, (+)-HA966 in a rat model of peripheral neuropathy. Br J Pharmacol. 1998 Dec;125(8):1641-50.

[ Density]:
1.436g/cm3

[ Boiling Point ]:
258.6ºC at 760mmHg

[ Molecular Formula ]:
C₄H₈N₂O₂

[ Molecular Weight ]:
116.11900

[ Flash Point ]:
110.2ºC

[ Exact Mass ]:
116.05900

[ PSA ]:
66.56000

[ Vapour Pressure ]:
0.002mmHg at 25°C

[ Index of Refraction ]:
1.59

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[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ RIDADR ]:
NONH for all modes of transport

Enantiomers of HA-966 (3-amino-1-hydroxypyrrolid-2-one) exhibit distinct central nervous system effects: (+)-HA-966 is a selective glycine/N-methyl-D-aspartate receptor antagonist, but (-)-HA-966 is a potent gamma-butyrolactone-like sedative.

Proc. Natl. Acad. Sci. U. S. A. 87 , 347, (1990)

The antagonist effect of (+/-)-3-amino-1-hydroxypyrrolid-2-one (HA-966) at the N-methyl-D-aspartate (NMDA) receptor occurs through a selective interaction with the glycine modulatory site within the r...

The discriminative stimulus properties of (+)-HA-966, an antagonist at the glycine/N-methyl-D-aspartate receptor.

Eur. J. Pharmacol. 186 , 129, (1990)

Using a two-lever operant drug discrimination paradigm, rats have been trained to discriminate between the administration of saline and R-(+)-HA-966 (R-(+)-3-amino-1-hydroxypyrrolid-2-one, 30 mg/kg i....

Stereoselectivity for the (R)-enantiomer of HA-966 (1-hydroxy-3-aminopyrrolidone-2) at the glycine site of the N-methyl-D-aspartate receptor complex.

J. Neurochem. 55 , 1346, (1990)

HA-966 (1-hydroxy-3-aminopyrrolidone-2) is an antagonist at the glycine allosteric site of the N-methyl-D-aspartate receptor ionophore complex. Unlike presently known glycine antagonists, HA-966 is ch...

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