(S)-(-)-HA-966

(S)-(-)-HA 966 ((-)-HA 966), a γ-Hydroxybutyrate-like agent, is weakly active as an NMDA-receptor antagonist. (S)-(-)-HA 966 possesses muscle relaxant action and prevents enhanced mesocorticolimbic dopamine metabolism and behavioral correlates of restraint stress, conditioned fear[1][2].

Signaling Pathways >> Neuronal Signaling >> iGluR

Research Areas >> Neurological Disease

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

On cultured cortical neurones (+)-HA-966 inhibits glycine-potentiated NMDA responses with an IC50=13 μM compared with (-)-HA-966 (IC50=708 μM)[2].

(S)-(-)-HA 966 ((-)-HA 966; 3 and 5 mg/kg; i.p.) prevents restraint stress-induced dopamine utilization in both the medial prefrontal cortex and nucleus accumbens. (S)-(-)-HA 966 suppresses fear-induced behaviors: immobility and defecation[1]. (S)-(-)-HA 966 (3 mg/kg; i.p.) prevents locomotor sensitization without altering the acute motoric response elicited by cocaine[1]. (S)-(-)-HA 966 (5 mg/kg; i.p.) blocks acute cocaine-induced locomotion but resulted in sedation[1].

[1]. B A Morrow, et al. (S)-(-)-HA-966, a gamma-hydroxybutyrate-like agent, prevents enhanced mesocorticolimbic dopamine metabolism and behavioral correlates of restraint stress, conditioned fear and cocaine sensitization. J Pharmacol Exp Ther. 1997 Nov;283(2):712-21.

[2]. L Singh, et al. 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. 1990 Jan;87(1):347-51.