Disease relevance of Eveite DOTG

• In contrast to the protection provided by the putative antagonists, the well-characterized sigma receptor agonist di-o-tolylguanidine (DTG) and the novel sigma receptor agonist BD1031 (3R-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane) each worsened the behavioral toxicity of cocaine [1].

High impact information on Eveite DOTG

• Protein phosphorylation and calcium uptake into rat forebrain synaptosomes: modulation by the sigma ligand, 1,3-ditolylguanidine [2].
• The sigma ligand 1,3-di-O-tolylguanidine (DTG) increased basal dynamin and decreased depolarization-stimulated phosphorylation of the synaptosomal protein synapsin Ib without having direct effects on protein kinases or protein phosphatases [2].
• Synthesis and in vitro evaluation of 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indoles: high-affinity ligands for the N,N'-di-o-tolylguanidine-labeled sigma binding site [3].
• In the presence of IC50 concentration (11 microM) of 1,3-di-o-tolylguanidine, no differences were found in the maximal number of muscarinic binding sites, whereas the dissociation constant increased approximately fivefold, indicating a decrease of the radioligand's affinity for the receptor [4].
• Synthesis and structure-activity relationships of N,N'-di-o-tolylguanidine analogues, high-affinity ligands for the haloperidol-sensitive sigma receptor [5].

Biological context of Eveite DOTG

• The current study investigated the effects of the acute s.c. and i.c.v. administration of 1,3-di-o-tolylguanidine (DTG) on body temperature in rats [6].

Anatomical context of Eveite DOTG

• Specific binding of [3H]-1,3-di-o-tolylguanidine (DTG) and (+)-[3H]-(3-hydroxyphenyl)-N-(1-propyl)-piperidine [(+)-3-PPP] to membranes of cultured cardiac myocytes from neonatal rats revealed the presence of sigma receptors on these cells [7].
• Repeated treatment with imipramine (10 mg/kg intraperitoneally (i.p.), once daily for 14 days) caused a decrease in the Bmax, without affecting the Kd, of [3H]DTG (1,3-di-o-tolylguanidine) binding to the haloperidol-sensitive sigma sites in the striatum, hippocampus and cerebral cortex of the rat [8].
• When haloperidol was preincubated (250 nM) with rat testis membranes, in order to mask the sigma sites, we observed that DTG (1,3-di-O-tolylguanidine) and haloperidol displayed a very low RBA (< 0.1%) and were not able totally to displace the [3H]RU 3117 binding up to 50 microM [9].
• The sigma ligand 1,3-di-o-tolylguanidine (DTG) has been applied by microiontophoresis to neurones in the rat hippocampal slice and to neurones in the neocortex and hippocampus of rats anaesthetised with urethane [10].
• In behavioral studies, BD1047 and BD1063 had no effects on their own when unilaterally microinjected into the red nucleus of rats, but both compounds attenuated the dystonia produced by the high affinity sigma ligands, di-o-tolylguanidine (DTG) and haloperidol [11].

Associations of Eveite DOTG with other chemical compounds

• An analog of 1,3-di-o-tolylguanidine (DTG), [125I]-labeled 1-(p-iodophenyl)-3-(1-adamantyl)guanidine (PIPAG), was synthesized as a potential ligand for cerebral sigma binding sites [12].
• Effects of subcutaneous and intracerebroventricular administration of the sigma receptor ligand 1,3-Di-o-tolylguanidine on body temperature in the rat: interactions with BMY 14802 and rimcazole [6].
• Repeated treatment with dl-pentazocine (5-10 mg/kg i.p.), but not d-methamphetamine (4.8 mg/kg i.p.), twice daily for 8 days diminished the specific [3H]1,3-di-o-tolylguanidine (DTG) binding to the haloperidol-sensitive sigma sites in rat striatum and hippocampus [13].
• Synaptosomes were prelabelled with 32P(i) and incubated with the sigma ligands 1,3-di-o-tolylguanidine (DTG), (+)pentazocine and (-)pentazocine (3, 10, 30, 100, 300 microM), or haloperidol, reduced haloperidol, and (+)SKF 10,047 (100 microM) [14].
• Pretreatment with 1,3-di-O-tolylguanidine (DTG), a ligand at both sigma 1 and sigma 2 sites, converted NMDA-induced desensitization to sensitization, thereby enhancing tonic NMDA receptor activity [15].

Gene context of Eveite DOTG

• BD1047 and BD1063 dose-dependently attenuated the dystonia produced by DTG, suggesting a receptor-mediated mechanism, and the dose curve for DTG was shifted to the right in the presence of the novel ligands [11].
• The sigma ligands, 1,3-di-o-tolylguanidine (DTG) and (-)-deoxy-N-benzylnormetazocine, produced a significant increase both in contralateral turning and in tyrosine hydroxylase activity [16].
• In radioligand binding experiments on membranes from human atrial appendages (alpha 2- and sigma-binding sites were masked), cannabinoid receptor ligands and IR agonists displaced the radiolabeled guanidine derivative [3H]DTG (1,3-di-o-tolyguanidine, an agonist at presynaptic IRs) from its binding sites [17].

Analytical, diagnostic and therapeutic context of Eveite DOTG

• Microinjection of the high affinity sigma ligands, di-o-tolylguanidine or haloperidol (0-10 nmol/0.5 microl), produced a marked increase in vacuous chewing and facial tremors in rats, while coadministration of the functional sigma antagonists, BD1047 or BD1063 (5 nmol), greatly attenuated these drug-induced movements [18].
• Pregnant rats were given 1,3-di-o-tolylguanidine (DTG) by gavage at 0, 10, 20 or 40mg/kgbw/day on days 6-19 of pregnancy and the pregnancy outcome was determined on day 20 of pregnancy [19].

References