2-hydroxysaclofen

2-Hydroxysaclofen is a potent γ-amino-butyric-acid-B (GABAB) receptor antagonist. 2-Hydroxysaclofen can abolish nicotine-induced hypolocomotor effects and increases the antinociceptive effects. 2-Hydroxysaclofen can stimulate luteinizing hormone (LH) secretion in female rats[1][2][3].

Research Areas >> Endocrinology

Signaling Pathways >> Membrane Transporter/Ion Channel >> GABA Receptor

Research Areas >> Neurological Disease

Signaling Pathways >> Neuronal Signaling >> GABA Receptor

GABAB receptor[1]

2-Hydroxysaclofen (0.25-1 mg/kg; IP; single dosage) abolishes nicotine hypolocomotor effects and increases the antinociceptive effects of nicotine[1]. 2-Hydroxysaclofen (0.3-3 mg/kg; IP; single dosage) reduces the effects of Baclofen (a GABA receptor agonist) on d-amphetamine-induced discriminative cue[2]. 2-Hydroxysaclofen (0-100 μg/2 μl; ICV; single dosage) produces a rapid elevation in the serum LH concentration in the estrogen-primed ovariectomized rat[3]. Animal Model: Male Swiss Webster mice (22-24 g; treated with 3 mg/kg nicotine)[1] Dosage: 0.25, 0.5 and 1 mg/kg Administration: IP; single dosage; after 10 or 45 min of nicotine administration Result: Abolished nicotine hypolocomotor effects at 1 mg/kg, and increased the antinociceptive effects of nicotine at 1 mg/kg. Animal Model: Male Wistar rats[2] Dosage: 0.3, 1 and 3 mg/kg Administration: IP; single dosage Result: Reduced the effects of Baclofen on d-amphetamine-induced discriminative cue. Animal Model: Female Wistar rats (8 weeks)[3] Dosage: 0, 20, 50 or 100 μg/2 μL Administration: ICV; single dosage Result: Produced a rapid elevation in the serum LH concentration in the estrogen-primed ovariectomized rat with a dose-dependent manner, and the peak LH values were observed 10 min after the injection. The effect was dose-dependent, as 0 or 20 μg of the antagonist was ineffective while a pronounced effect was observed after the injection of 50 or 100 μg.

[1]. Varani AP, et al. Baclofen and 2-hydroxysaclofen modify acute hypolocomotive and antinociceptive effects of nicotine. Eur J Pharmacol. 2014 Sep 5;738:200-5.

[2]. Miranda F, et al. The GABA-B antagonist 2-hydroxysaclofen reverses the effects of baclofen on the discriminative stimulus effects of D-amphetamine in the conditioned taste aversion procedure. Pharmacol Biochem Behav. 2009 Jul;93(1):25-30.

[3]. Akema T, et al. 2-Hydroxysaclofen, a potent GABAB receptor antagonist, stimulates luteinizing hormone secretion in female rats. Brain Res. 1991 Apr 12;546(1):143-5.