N,N'-monomethylenebis(pyridiniumaldoxime): RN given refers to parent cpd [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
| ID Source | ID |
|---|---|
| PubMed CID | 135464156 |
| CHEMBL ID | 1181952 |
| MeSH ID | M0047103 |
| Synonym |
|---|
| n,n'-monomethylenebis(pyridiniumaldoxime) |
| CHEMBL1181952 |
| 1,1'-methylenebis(4-((hydroxyimino)methyl)-pyridinium) |
| 61444-84-6 |
| mmb 4 |
| pyridinium, 1,1'-methylenebis(4-((hydroxyimino)methyl)- |
| 1,1'-methylenebis(4-((hydroxyimino)methyl)pyridinium) |
| DTXSID00210389 |
| Excerpt | Reference |
|---|---|
| " Adverse clinical observations were noted in the rats at ≥ 400 mg/kg/d and in rabbits administered ≥ 200 mg/kg; no adverse findings were noted in the monkeys." | ( Comparative toxicology studies in Sprague-Dawley rats, rhesus monkeys, and New Zealand White rabbits to determine a no observed adverse effect level for 1,1'-methylenebis[4-[(hydroxyimino)methyl]-pyridinium] dimethanesulfonate. Buccellato, M; Burback, BL; Croutch, CR; Elcock, LE; Johnson, JD; Kobs, DJ; Osheroff, MR, ) |
| " In the ED50 study, male guinea pigs clipped of hair received 2x LD50 topical challenges of undiluted Russian VX (VR), VX, or phorate oxon (PHO) and, at the onset of cholinergic signs, IM therapy of atropine (0." | ( Toxicity and median effective doses of oxime therapies against percutaneous organophosphorus pesticide and nerve agent challenges in the Hartley guinea pig. Babin, MC; Jett, DA; Platoff, GE; Snider, TH; Yeung, DT, 2016) |
| Excerpt | Reference |
|---|---|
| " Plasma concentrations for both oximes were fitted to standard pharmacokinetic models using the computer program PCNONLIN." | ( Pharmacokinetics and pharmacodynamics of oximes in unanesthetized pigs. Corcoran, KD; Hayward, IJ; Kaminskis, A; McCluskey, MP; Shih, ML; Stemler, FW; Stewart, JR; Tezak-Reid, TM; Wade, JV, 1991) |
| " Kinetic data in the scientific literature for MMB-4 are limited; therefore, a physiologically based pharmacokinetic (PBPK) model was developed for a structurally related oxime, 1,1'-trimethylenebis{4-hydroximinomethyl}pyridinium dibromide." | ( A physiologically based pharmacokinetic model for the oxime TMB-4: simulation of rodent and human data. Covington, TR; Gearhart, JM; Ruark, CD; Sterner, TR; Yu, KO, 2013) |
| " The present study characterized pharmacokinetic (PK) profiles of MMB4 in male and female Sprague-Dawley rats, New Zealand White rabbits, and beagle dogs given a single intravenous (IV) administration of MMB4 dimethanesulfonate (DMS) at 55, 25, and 15 mg/kg dose, respectively." | ( Pharmacokinetics of MMB4 DMS in rats, rabbits, and dogs following a single IV administration. Burback, BL; Gibbs, ST; Hong, SP; Johnson, JD; Kobs, DJ; Osheroff, MR, ) |
| Excerpt | Reference |
|---|---|
| "The effect of methoxime combined with a) atropine, b) benactyzine, c) atropine and natrium thiosulphate, d) atropine and diazepam on antidotal treatment effectiveness was studied in tabun-poisoned mice." | ( Effect of methoxime combined with anticholinergic, anticonvulsant or anti-HCN drugs in tabun-poisoned mice. Sevelová, L; Vachek, J, 2003) |
| "We evaluated the efficacy of aerosolized acetylcholinesterase (AChE) reactivator oxime MMB-4 in combination with the anticholinergic atropine sulfate for protection against respiratory toxicity and lung injury following microinstillation inhalation exposure to nerve agent soman (GD) in guinea pigs." | ( Aerosolized delivery of oxime MMB-4 in combination with atropine sulfate protects against soman exposure in guinea pigs. Doctor, BP; Nambiar, MP; Oguntayo, S; Perkins, MW; Pierre, Z; Sabnekar, P; Sciuto, AM; Song, J; Soojhawon, I, 2012) |
| Excerpt | Reference |
|---|---|
| " Preliminary preclinical in vivo studies have demonstrated that all concentrations and particle sizes have desirable PK properties, including high bioavailability and rapid absorption, which is critical to combat potent and fast-acting nerve agents." | ( MMB4 DMS nanoparticle suspension formulation with enhanced stability for the treatment of nerve agent intoxication. Cabell, LA; Clark, AP; Dixon, H; McDonough, JA, ) |
| " The MMB4 DMS was extensively absorbed into the systemic circulation after IM administration as demonstrated by greater than 80% absolute bioavailability values for rats, rabbits, and dogs." | ( Comparative toxicokinetics of MMB4 DMS in rats, rabbits, dogs, and monkeys following single and repeated intramuscular administration. Burback, BL; Croutch, CR; Gibbs, ST; Hawk, MA; Hong, SP; Johnson, JD; Kobs, DJ; Osheroff, MR, ) |
| Excerpt | Reference |
|---|---|
| " Rats received DFP intraperitoneally in a dosage of 6, 8, or 10 micromol/rat and immediately thereafter intraperitoneal injections of K-27, K-48, pralidoxime, obidoxime, trimedoxime, methoxime, or HI-6." | ( Efficacy of two new asymmetric bispyridinium oximes (K-27 and K-48) in rats exposed to diisopropylfluorophosphate: comparison with pralidoxime, obidoxime, trimedoxime, methoxime, and HI-6. Hasan, MY; Kuca, K; Lorke, DE; Nurulain, SM; Petroianu, GA; Schmitt, A, 2009) |
| " The PBPK model can be used to optimize the dosing regimen to improve oxime therapeutic efficacy in a human population." | ( A physiologically based pharmacokinetic model for the oxime TMB-4: simulation of rodent and human data. Covington, TR; Gearhart, JM; Ruark, CD; Sterner, TR; Yu, KO, 2013) |
| " Pulmonary function was evaluated for the first 5 hours after concurrent dosing with cardiovascular monitoring; then cardiovascular monitoring continued for 72 hours after dosing." | ( MMB4 DMS: cardiovascular and pulmonary effects on dogs and neurobehavioral effects on rats. Burback, BL; Hassler, CR; Hawk, MA; Osheroff, MR; Pressburger, DT; Ritchie, GD; Roche, BM; Vinci, TM, ) |
| " For both animal species, the majority of the total radioactivity was excreted in the urine (74%-94%) by 72 hours after dosing with greater than 90% of the radioactivity measured in the urine within 8 to 12 hours after dosing." | ( Absorption, distribution, metabolism, and excretion of 14C-MMB4 DMS administered intramuscularly to Sprague-Dawley rats and New Zealand White rabbits. Burback, BL; Hong, SP; Johnson, JD; Kobs, DJ; Lusiak, BD, ) |
| "Acetylcholinesterase (AChE) reactivation studies were conducted in guinea pigs (GPs) and nonhuman primates (NHPs) to determine the 1,1'-methylenebis{4-[(hydroxyimino)methyl] pyridinium} dimethanesulfonate (MMB4 DMS) dose that reactivated at least 20% of blood AChE within 15 minutes following cyclosarin (GF) dosing (used as the criterion for efficacy)." | ( In vivo acetylcholinesterase reactivation in male guinea pigs and rhesus macaques following cyclosarin exposure and treatment with 1,1'-methylenebis{4-[(hydroxyimino)methyl] pyridinium} dimethanesulfonate. Harvilchuck, JA; Hong, SP; Johnson, JD; Osheroff, MR; Richey, JS, ) |
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID1173375 | Reactivation of tabun-inhibited human acetylcholinesterase at 1 mM in pH 7.4 phosphate buffer at 37 degC by Ellman's method | 2014 | Bioorganic & medicinal chemistry letters, Dec-15, Volume: 24, Issue:24 | New efficient imidazolium aldoxime reactivators for nerve agent-inhibited acetylcholinesterase. |
| AID1173371 | Reactivation of sarin-inhibited human acetylcholinesterase at 1 mM in pH 7.4 phosphate buffer at 37 degC by Ellman's method | 2014 | Bioorganic & medicinal chemistry letters, Dec-15, Volume: 24, Issue:24 | New efficient imidazolium aldoxime reactivators for nerve agent-inhibited acetylcholinesterase. |
| AID1173376 | Reactivation of tabun-inhibited human acetylcholinesterase at 0.1 mM in pH 7.4 phosphate buffer at 37 degC by Ellman's method | 2014 | Bioorganic & medicinal chemistry letters, Dec-15, Volume: 24, Issue:24 | New efficient imidazolium aldoxime reactivators for nerve agent-inhibited acetylcholinesterase. |
| AID1173374 | Reactivation of VX-inhibited human acetylcholinesterase at 0.1 mM in pH 7.4 phosphate buffer at 37 degC by Ellman's method | 2014 | Bioorganic & medicinal chemistry letters, Dec-15, Volume: 24, Issue:24 | New efficient imidazolium aldoxime reactivators for nerve agent-inhibited acetylcholinesterase. |
| AID1173373 | Reactivation of VX-inhibited human acetylcholinesterase at 1 mM in pH 7.4 phosphate buffer at 37 degC by Ellman's method | 2014 | Bioorganic & medicinal chemistry letters, Dec-15, Volume: 24, Issue:24 | New efficient imidazolium aldoxime reactivators for nerve agent-inhibited acetylcholinesterase. |
| AID1173372 | Reactivation of sarin-inhibited human acetylcholinesterase at 0.1 mM in pH 7.4 phosphate buffer at 37 degC by Ellman's method | 2014 | Bioorganic & medicinal chemistry letters, Dec-15, Volume: 24, Issue:24 | New efficient imidazolium aldoxime reactivators for nerve agent-inhibited acetylcholinesterase. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 2 (5.00) | 18.7374 |
| 1990's | 6 (15.00) | 18.2507 |
| 2000's | 12 (30.00) | 29.6817 |
| 2010's | 17 (42.50) | 24.3611 |
| 2020's | 3 (7.50) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 0 (0.00%) | 5.53% |
| Reviews | 1 (1.85%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 53 (98.15%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||