Disease relevance of NC-758

• Thus, the activating effects of homotaurine in this epilepsy model are in keeping with the demonstrated GABAmimetic properties of the compound [1].
• Taurine, homotaurine, GABA and muscimol, given intraventricularly to the conscious, unrestrained rabbit cause hypothermia and a reduction in skeletal muscle tone [2].
• Homotaurine induced dose-dependent hypotension and bradycardia when given i.v. and i.c.v. It was, however, more effective when injected i.c.v., and the decrease in ventilatory tidal volume occurred after i.c.v. administration of homotaurine only [3].

Psychiatry related information on NC-758

• However, GABAB receptor antagonists, such as homotaurine and delta-amino-n-valeric acid, reversed the catatonia induced by baclofen in rats [4].
• The effects of homotaurine are less important on the wakefulness, but it also increases the percentage of REMS without influencing its latency of appearance [5].
• Agonists differed one from another in their effects on variable-interval self-stimulation: clonazepam (in repeatedly-tested rats), chlordiazepoxide and pentobarbitone had a strongly biphasic action, low doses being facilitatory and high doses depressant, whereas other agonists including valproate and 3-APS (homotaurine) were uniformly depressant [6].
• This article reviews the unique mode of action of tramiprosate and summarizes the available clinical information on the effects of tramiprosate in patients with Alzheimer's disease [7].

High impact information on NC-758

• In vivo, homotaurine and baclofen caused aggregation of pigment in dermal melanophores [8].
• The GABAA-receptor agonists muscimol and 3-aminopropanesulphonic acid (3-APS), a low dose of pentobarbitone, diazepam and picrotoxin (PTX) potentiated control head-twitch rates but had no further effect when head-twitching had been potentiated by FLA-63 [9].
• Following intrathecal injection, pretreatment with both D-baclofen and 5-aminovaleric acid (5-AV) inhibited the antinociceptive effect of L-baclofen, but homotaurine (3-aminopropane sulphonic acid, APS) was inactive as an antagonist (rank order D-baclofen greater than 5-AV greater than APS = 0) [10].
• Homotaurine: a GABAB antagonist in guinea-pig ileum [11].
• Somewhat surprisingly, TAG also offset the inhibitory effects on cortical cells and the dorsal root depolarizing actions of muscimol, 3-aminopropane sulfonic acid and piperidine-4-sulfonic acid, all of which heretofore have been considered as selective gamma-aminobutyric acid agonists [12].

Biological context of NC-758

• Homotaurine led to a dose-related fall in blood pressure and heart rate; maximum effects were obtained with 300 microgram/kg and averaged 55 +/- 3 mm Hg and 73 +/- 3 beats/min [13].
• Both taurine and homotaurine (t00 mg/kg each) inhibited intestinal absorption of cholesterol [14].

Associations of NC-758 with other chemical compounds

• This action of GABA was mimicked by the GABA-T antagonists aminooxyacetic acid and ethanolamine-O-sulphate, but not by the GABA analogues muscimol, 3-aminopropanesulphonic acid, gamma-hydroxybutyrate or beta-(p-chlorophenyl)-GABA [15].
• Cyclic amidine analogues of taurine and homotaurine: synthesis and effects on rat skeletal muscle [16].

Gene context of NC-758

• One amyloid-binding drug, tramiprosate (3-amino-1-propanesulfonic acid; Alzhemed), which is effective in reducing polymerisation in vitro and plaque deposition in animals, has now reached phase III clinical trials [17].
• Only homotaurine elevated serum prolactin of male rats at this dose, but its effect was less pronounced (p < 0.01) in male than in female rats [18].

Analytical, diagnostic and therapeutic context of NC-758

• Role of K+ -channels in homotaurine-induced analgesia [19].
• The results have been compared with a control group of 36 rats that received water during the treatment phase of the experiment, and the 14th day received intraperitoneal muscimol or homotaurine [5].
• CGP 35348 (50-200 mg/kg IP), a highly selective GABA(B) antagonist, was administered prior to carrying out a dose-response curve of homotaurine (22.6-445 mg/kg IP) antinociceptive effect in the abdominal constriction (mice) and tail flick (rats) tests [20].
• Promising findings for the efficacy of tramiprosate, indicated by improvement or stabilization of cognitive function, have been shown in phase II clinical trials and open-label extensions of these studies [7].
• Uptake, autoradiography and release of taurine and homotaurine from retinal tissue [21].

References