Therapeutic effects of HS-3, HS-6, benactyzine, and atropine in soman poisoning of dogs

Abstract

Investigations into the therapeutic properties of various combinations of the bispyridinium salts HS-3 and HS-6 and the cholinolytics atropine and benactyzine against soman poisoning in unanesthetized male beagles were performed. In our investigations we observed that: 1. The most effective protection against soman poisoning was attained if both oximes were applied early i.m. 6 min after intoxication together with the cholinolytics. 2. On the basis of clinical symptoms HS-6 proved to have a more intensive therapeutic effect than HS-3 upon early application. 3. If HS-3 was applied early after s.c. intoxication with low concentrations of soman (up to 3 LD50), a significant protection or reactivation effect on serium cholinesterase was measured. 4. When HS-3 was applied at the beginning of convulsions--generally 28 min after s.c. intoxication--it also raised the rate of surviving animals. 5. The maximal blood levels for HS-3 and HS-6 were measured 20-30 min after i.m. injection; the half-life values of HS-3 and HS-6 in plasma were 45-60 min.

Cholinesterase activity as biomarker of neurotoxicity: utility in the assessment of aquatic environment contamination

“…It is proposed that benactyzine has more efficiency in preventing somaninduced convulsions in the tested animals. When benactyzine is used, cholinolytic agent is not necessary (46). But our investigation on the effect of benactyzine on human serum BChE showed that benactyzine and drofenine are competitive inhibitors of the enzyme.…”

The ganglionic blocking properties of the cholinesterase reactivator, HS-6

“…( 1976 ) used atropine plus 100 mg/kg i.v. HS-6 In the treatment of rĩts against soman , while Schenk et al (1976) used a regimen containing 100 mg/kg i.m. HS-6 in dogs.…”

“…From the literature , two doses of HS-6 were selected for study to examine some of the cardiovascular effects of HS-6 (Schenk et al, 1976;Wol thuis et al ., 1976). HS-6 or other compounds were injected via the femoral vein and the changes i n soñe cardiovascular and respiratory parameters recorded .…”

“…Some organophosphates such as soman ~o -pinacoly1-methyl phosphonofluoridate) produce an inhibited chol inesterase which rapidly ages , rendering the inhibited enzyme refractory to reactivation by the oximes mentioned previously. However, the use of cholinolytics with oximes such as HS-6 , 1(2 -hydroxyimino-methyl)-pyridinium-(l)-methyl]-L (3-carbamyl )-pyridinium-(1) methyl J-ether dichlorlde (Figure 1) , have been shown to produce success in protecting animals from several LD 50 s of soman, but the mechanism of this protective effect is not yet clear (Oldige s and Schoene, 1970;Schenk et al, 1976;Woi thuis et al, 1 976).…”

The Mechanism of Interaction of Oximes with the Muscarinic-Cholinergic Complex in the Central Nervous System

“…Recovery from such poisoning can be achieved by administration of a mixture of muscarinic antagonists and oximes, provided that the phosphoryl-enzyme can be reactivated by the latter. Several organophosphates (such as soman) form a phosphoryl-enzyme adduct which is not reactivated by oximes (4,5), yet the mixture of some oxime/antagonists is still useful in partial protection against saman intoxication (6)(7)(8)(9)(10). This phenomenon led to the idea that oximes may act via the mu'carinic cholinergic receptor, in conjunction with the muscarinic antagonist.…”