Effect of PAM-2 and TMB-4 on the activity of »arminase«

Proučeno je in vitro dejstvo PAM-2 i TMB-4 na aktivnost »arminaze« u plazmi zeca. Koncentracija od 1.10-3M PAM-2 i TMB-4 nema nikakvo dejstvo na aktivnost »arminaze«. Nikakvo dejstvo nije zapaženo niti kad se primene zajedno sa aktivatorom (NaF) ili inhibitorom (SKF-525 A) »arminaze«.In vitro studies have been carried out concerning the effect of P AM-2 and TMB4 on the activity of »arminase« in the rabbit\u27s plasma. The concentration of 1.10-3M of PAM-2 and TMB-4 produced no effect on the »arminase« activity. No effect was observed either when PAM-2 and TMB-4 were applied together with an activator (NaF) or inhibitor (SKF-525 A) of »arminase«

Syntheses and Spectrophotometric Studies of Some New Aralkyl Pyridinium Oximes

Syntheses and some physical properties of seven aralkyl pyridinium oximes, potential antidotes against organophosphorus poisons and potential reagents for pentacyano compounds of iron, are described and discussed. Their UV absorption spectra in water and in water-dioxane solutions at different pH values have been measured. The spectral changes with changing pH in aqueous solutions are attributed to the dissociati.on of individual functional groups of the compounds, and in water-dioxane mixtures they are attributed to the polarities of the solvents. One equilibrium is established in most of the compounds, however, in PhPA-4 and PhOPA-4 two equilibria exist. The dissociation constants of all compounds have been determined spectrophotometrically. The pK\u27s of the compounds are discussed in terms of the structure of the compounds. A spectrophotometric method for the determination of the examined compounds is proposed

Preparation of γ-di-tertiary Glycols From the Esters of γ-keto Carboxylic Acids. II

Some Y-di-tertiary glycols have been prepared by the Grignard\u27s method from the Et esters of y-keto carboxylic acids

Syntheses and Spectrophotometric Studies of Some New Aralkyl Pyridinium Oximes

Syntheses and some physical properties of seven aralkyl pyridinium oximes, potential antidotes against organophosphorus poisons and potential reagents for pentacyano compounds of iron, are described and discussed. Their UV absorption spectra in water and in water-dioxane solutions at different pH values have been measured. The spectral changes with changing pH in aqueous solutions are attributed to the dissociati.on of individual functional groups of the compounds, and in water-dioxane mixtures they are attributed to the polarities of the solvents. One equilibrium is established in most of the compounds, however, in PhPA-4 and PhOPA-4 two equilibria exist. The dissociation constants of all compounds have been determined spectrophotometrically. The pK\u27s of the compounds are discussed in terms of the structure of the compounds. A spectrophotometric method for the determination of the examined compounds is proposed

The use of a new compound - TMB-4 Cl2 - in the protection of armin poisoned mice

Ispitao je TMB-4 CJ2 [1,3-trimetilcnbis(4-formil piridinijum hlorid) dioksim] kao zaštitno sredstvo kod miševa otrovanih arminom. TMB-4 Cl2, t. t. 235° C (nekor.), dobiven je iz TMB-4 [l,3-trimetilen-bis( 4-fonnilpiridinijum bromid)dioksim] i AgCI. Molekularni ekstinkcioni koeficijenat na 280 mµ je 32380, pK = 8,28; rastvorljivost u vodi 2 : 3. LD50 za bele miševe mužjake i ženke iznosi 88 (73-105) mg/kg. Zaštitna moć kod miševa otrovanih arminom i reaktivatorsko dejstvo na ChE celokupne krvi i mozga otrovanih miševa in vivo i na inhibiranu ChE plazme i eritrocita zeca in vitro isti su kao i rezultati koje su autori ranije objavili istražujući zaštitno dejstvo TMB-4.The protective effect of TMB-4 Cl2 [1,3-trimethylene bis (4-formil pyridine chloride) dioxime] in mice poisoned by armin [4-fonnyl (ethyl-p-nitrophenyl ethylphosphonate)] was studied. TMB-4 Cl2, m. p. 235° C (uncor.) was obtained from TMB-4 [1,3-trimethylene his (4-formyl pyridine bromide) dioxime] and AgCI. The molecular extinction per 280 mµ was 32380, pK = 8.28; solubility in water 2:3, LD50 in male and female albino mice was 88 (73-105) mg/kg. The protective effect of TMB-4 CI2 on armin poisoned mice and its reactivation effect on ChE of the whole blood and the brain of the poisoned mice in vivo, as well as on the inhibited ChE of the plasma and erythrocytes of the rabbits in vitro have proved the same as the effects obtained by the authors in the earlier experiments with TMB-4

Preparation of γ-di-tertiary Glycols From the Esters of γ-keto Carboxylic Acids. II

Some Y-di-tertiary glycols have been prepared by the Grignard\u27s method from the Et esters of y-keto carboxylic acids

The therapeutic effect of PAM-2 Cl on armin poisoned mice

PAM-2 CI (piridin-2-aldoksim metilhiorid) dobiven je propuštanjem rastvora PAM-2 (piridin-2-aidoksim metiljodid) kroz anionski izmjenjivač Duolit A-30 ili kuhanjem zasićenog rastvora PAM-2 sa AgCI. Iskorištenje 35-50%, t. t. 218-20° C (nekor). Rastvorljivost u vodi 50%. Koncentracija od 1.10-3M PAM-2 CI dovodi do 25% inhibicije ChE plazme i eritrocita zeca, a koncentracija od 1.10-4M dovodi kroz Ih do 800/o reaktivacije ChE plazme i eritrocita zeca (kunića) inhibiranih arminom. Iste vrednosti dobivene su i sa PAM-2. Zaštitno dejstvo PAM-2 CI kod miševa otrovanih arminom jednako je dejstvu PAM-2 i u odnosu na dozu i u odnosu na vreme aplikacije.PAM-2 Cl (pyridine-2-aldoxime methyl chloride) was obtained by allowing the solution of PAM-2 (pyridine-2-aldoxime methyl iodide) to pass through the anion exchanger Duolit A-30 or by boiling a saturated PAM-2 solution with AgCI. The yield was 35-50%, m. p. 218-220° C (uncor.), solubility in water 1:1. The concentration of 1.10-4 PAM-2 Cl produces a 25% inhibition of the rabbit\u27s plasma and erythrocyte ChE. The concentration of 1.10-4 PAM-2 Cl produces, in an hour, 80% reactivation of the same enzymes inhibited by armin (ethyl-p-nitrophenyl ethylphosphonate). The same results were obtained with PAM-2. The protective effect of P AM-2 Cl on the mice poisoned by armin is equal to that of PAM-2 regarding both the dose and the time of application

Direct interaction of pyridinium oximes with organophosphorus compounds

Ispitana je in vitro interakcija devet mono- i bis-piridinijskih mono- i dioksima sa tabunom, sarinom. somanom i VX. Reakcija je praćena spektrofotometrijski u pH 7,7 na 37 ºC pri koncentraciji oksima 5x10-5 mol/L i koncentraciji organofosfata 8x10-4 mol/L. Oksimi se najbrže fosforilišu tabunom i sarinom (t/2 = 3,4-16,7 min), nešto sporije somanom (·t/2 = 14.4-22.5 min), a veoma sporo ako se upotrebi VX (t/2 = 191,1-457,5 min). S obzirom na to da su konstante brzine izračunate na reakcije samo jedne koncentracije otrova i jedne koncentracije oksima, koje nisu identične koncentracijama u in vivo eksperimentu, teško je proceniti povezanost fosforilacije in vitro i efikasnosti oksima in vivo.A direct interaction of organophosphorus nerve agents sarin, tabun, soman and VX with nine quaternated pyridinium aldoximes was studied in vitro. The kinetics of the reaction (kobs) was measured by UV spectrophotometry from decrease in oxime concentration. At an oxime concentration of 5 x 10-5 mol/L and organophosphate concentration of 8 x 10-4 mol/L, at pH 7.7 the half-period of the reaction between oximes and sarin or tabun was between 3.4 and 16.7 min. The half-period of the reaction between oximes and soman was slightly increased (14.4-22.5 min), and between oximes and VX it was greatly increased (191.1-457.5 min). Considering that the reaction rate constants were calculated from the reaction of only one organophosphate and one oxime concentration, which were not identical with those in viva, it is difficult to estimate to what extent these reactions may be useful in the therapy of intoxication by nerve agents

In vitro and in vivo Reactivation of Cholinesterases Inhibited by Highly Toxic Organophosphorus Compounds

The in vitro and in vivo reactivating power of 1,3-acetone- bis-(4-hydroxyiminoformyl pyridinium) dibromide (MBM-3) was compared with that of 1,3-trjmethylene~bis-(4-hydroxyjminoformyl pynidinium) dibromide (TMB-4) and 1,3-dimethylether-bis-(4-hydroxyiminoformyl pyridinium) dibromide (Toxogonin). As a source of choli\u27nesterase rat\u27s whole blood, plasma, erythrocytes, and brain ho~ mogenate, were u sed. The cholinesterase inhibition was performed by ethyl N-dimethylaminophosphorocyanidate (Taibun); ethyl 4- -nitrophenyl phosphonate (Armin), 0,0-diethyl-S-(2-diethylaminoethyl) phosphorothioate (Amitone-3); pinacolyl-methyl-phosphorofluoridate (Soman); and O-ethyl-S-(2-diethylamino ethyl phosphorothioate (Edemo-3)

Djelovanje mono-kvaternernih i bis-kvaternernih piridinijumskih oksima na akutnu toksičnost i antiholinesterazno djelovanje karbarila, dioksakarba i karbofurana

The acute toxicities of insecticidal carbamates (Dioxacarb, Carbaryl and Carbofuran) were determined in mice by s. c. or i. p. injection, both in the absence and in the presence of atropine and several pyridinium oximes. Atropine had a beneficial effect on the toxicity of all the three carbamates, while the oximes varied in their effects. In the case of Carbaryl all oximes used increased its toxicity, while in Dioxacarb and Carbofuran poisoning some of them were effective. It was found that the oximes do not influence the action of carbamates on the activity of serum cholinesterase in vitro, in a way which could explain their effect on the toxicity of these compounds. It is concluded, that the use of oximes is contraindicated in cases of intoxication with Carbaryl, Dioxacarb and Carbofuran.Ispitana je akutna toksičnost karbamatnih insekticida dioksarba, karbarila i karbofurana (LD-50) s. c. ili i. p., sa simultanom primjenom atropina ili bez nje i nekoliko piridinijumskih oksima. Atropin je pokazao povoljan efekat u trovanjima sa sva tri karbamata, dok je djelovanje oksima bilo različito. U trovanjima karbarilom i karbofuranom gotovo svi oksimi su potencirali njihovo toksično djelovanje, dok su u trovanju dioksakarbom neki bili djelotvorni. Oksimi ne utiču na inhibiciju holinesteraze in vitro ovim karbamatima na način kojim bi se moglo rastumačiti njihovo in vivo djelovanje. Na temelju eksperimenata je zaključena da je upotreba oksima u trovanju karbarilom, dioksakarbom i karbofuranom kontraindikovana