Disease relevance of 117354-64-0

• This action was blocked by 2-OH-saclofen (200 microM) and also by pretreatment of the cultures with pertussis toxin.(ABSTRACT TRUNCATED AT 400 WORDS)[1]
• Both baclofen-induced hyperpolarization and respiratory depression were antagonised by 2-OH-saclofen, which did not affect respiration-related IPSPs per se [2].
• Blockade of GABAA receptors by infusion of (-)-bicuculline (25 ng) had no effect on the decrease in body temperature elicited by MSO, but blockade of GABAB receptors by infusion of 2-OH-saclofen (13.3 ng) significantly attenuated MSO-induced hypothermia [3].
• However, sustained potentiation could not be induced in the presence of the GABAB-receptor antagonists 2-OH-saclofen (400 microM) or CGP35348 (3-amino-propyl-(diethoxymethyl)phosphinic acid, 100 microM), although a subsequent tetanus following washout induced sustained potentiation [4].
• Ipsilateral intra-NTS microinjection of BMI (10 pmol) or the GABAB-antagonist, 2-OH-saclofen (400 pmol), attenuated the tachycardia elicited from the DMN [5].

Psychiatry related information on 117354-64-0

• Results showed that phaclofen, 2-hydroxysaclofen, BPBA and baclofen all dose-dependently decreased ethanol-induced locomotor activity, and, of these, baclofen and BPBA did so at doses which did not attenuate locomotor activity when administered alone [6].

High impact information on 117354-64-0

• Moreover, the GABAB receptor agonist baclofen, and the antagonist 2-hydroxysaclofen had no effect [7].
• GABA, bicuculline (a GABAA receptor blocker), and 2-hydroxysaclofen (a GABAB receptor blocker) were directly infused into the stalk-median eminence while perfusates were collected for LHRH determination [8].
• Baclofen action is inhibited by the GABABR antagonist, 2-hydroxysaclofen [9].
• However, 2-OH-saclofen had lesser effects on the second late EPSP elicited during paired-pulse stimulation [10].
• 3 Stimulatory effects of SKF-97541 (0.1 mg kg(-1), i.v.) were blocked by the selective GABAB antagonist, 2-hydroxysaclofen, cholinergic blockade with atropine, subdiaphragmatic vagotomy or gastrin immunoneutralization [11].

Chemical compound and disease context of 117354-64-0

• Post- but not presynaptic effects of baclofen were blocked by 2-hydroxy-saclofen (100 microM) and pertussis toxin pretreatment [12].

Biological context of 117354-64-0

• 2-Hydroxy-saclofen is known to be active at GABAB receptors in the mammalian central nervous system, and we have investigated its effects on synaptic transmission in the rat hippocampal slice preparation [13].
• GABAB receptor blockade by 2-hydroxysaclofen reduced the respiratory frequency but increased the peak amplitude of respiratory bursts [14].
• Coinjection of the GABAB receptor antagonist 2-hydroxysaclofen 100 or 200 pmol had no significant effect on the heart rate response to BMI, but reversed the suppression elicited in the presence of baclofen [15].

Anatomical context of 117354-64-0

• Baclofen reversibly reduced the amplitude of excitatory postsynaptic currents evoked by optic nerve stimulation and the effect was antagonized by 2-hydroxysaclofen [16].
• The iontophoretic administration of the GABAB antagonists (P-(3-aminopropyl)-P-diethoxymethyl-phosphinic acid (CGP 35348) and 2-hydroxy-saclofen blocked the action of iontophoretically applied L-baclofen on neurons in the trigeminal nucleus of rats, anesthetized with halothane [17].
• In the presence of the GABA(B) antagonist 2-hydroxysaclofen (100 microM), but not in its absence, stimulation of the dorsal root at 1 or 10 Hz was able to elicit internalization, which was not inhibited by the NMDA receptor antagonist AP-5 (50 microM) or the channel blocker MK-801 (10 microM) [18].
• Saclofen (the direct sulphonic analogue of baclofen) is a competitive antagonist of baclofen at GABAB receptors in guinea pig ileum and rat cortical slices (estimated pA2 = 5.3), at least twice as potent as 2-hydroxy-saclofen (pA2 = 5) [19].
• The actions of 2-hydroxy-saclofen at presynaptic GABAB receptors in the rat hippocampus [20].

Associations of 117354-64-0 with other chemical compounds

• It was not greatly affected by the perfusion of 6-cyano-7-nitroquinoxaline-2,3-dione (10-20 microM), while it was potentiated in the presence of bicuculline methiodide (30 microM) or picrotoxin (50-100 microM) and 2-hydroxysaclofen (100-300 microM) [21].
• The i.p. pretreatment of animals with 6-hydroxydopamine (100 mg/kg) for 3 days significantly inhibited SR-95,531 (3 ng i.c.v.)- but not 2-hydroxysaclofen (10 microg i.c.v.)-induced increase in the basal plasma IL-6 levels [22].
• The blockade of the 2-hydroxy-saclofen effect by phaclofen implies a GABAB receptor partial agonist action [13].
• Prior combined microinjections of GABA(A) and GABA(B) receptor antagonists (2 mmol/l gabazine and 100 mmol/l 2-hydroxysaclofen, respectively) into the mNTS blocked the responses to microinjections of nociceptin at the same site [23].
• The effects of local pressure application of the selective GABA(A) antagonists, bicuculline, gabazine, and picrotoxin, and the selective GABA(B) antagonists, 2-OH-saclofen and CGP-55845A, on the spontaneous activity of electrophysiologically identified substantia nigra dopaminergic neurons were recorded in vivo in urethane anesthetized rats [24].

Gene context of 117354-64-0

• 2-(3-Carboxyl)-3-amino-6-(4-methoxyphenyl)-pyridazinium bromide (SR-95,531; 0.3-10 ng), a GABAA receptor antagonist, and 2-hydroxysaclofen (1-10 microgram), a GABAB receptor antagonist, injected i.c.v. increased both the basal and the restraint stress-induced plasma IL-6 levels [22].
• The intrathecal administration of 2-hydroxysaclofen, a GABAB receptor antagonist, had no effect [25].
• In addition, the GABAB receptor antagonist, 2-hydroxysaclofen, or the metabotropic Glu receptor type 4 antagonist, alpha-methylserine-O-phosphate, did not change either the latency or the maximal slope [26].
• The effect of GABA was concentration-dependent (1-1000 microM) and was blocked by a GABAA receptor antagonist, bicuculline (100 microM), or a GABAA chloride channel blocker, picrotoxin (100 microM), but not by a GABAB receptor antagonist, 2-hydroxysaclofen (100 microM) [27].

Analytical, diagnostic and therapeutic context of 117354-64-0

• Focal electrical stimulation produced a hyperpolarizing synaptic potential that was reduced by 75-95% by the GABAB-receptor antagonist 2-hydroxysaclofen (300 microM) [28].
• Unilateral microinjections of the GABA(B) receptor antagonist 2-hydroxysaclofen into the ventromedial thalamic nucleus ipsilateral to the nigrostriatal lesion induced contralateral rotations in a dose-dependent manner [29].
• Iontophoresis of another GABA(B) receptor antagonist, 2-OH-saclofen, also had no significant effect on visual response amplitude and pattern adaptation [30].

References