Prophylaxis carbamates

The effect on soman toxicity by pyridostigmine prophylaxis in different species could in principle also be explained by the CarbE concept of Sterri and Fonnum (1989). This means that the protection factors of carbamate prophylaxis as calculated for the different species were similar to the experimental protection factors of pyridostigmine prophylaxis against soman as observed for rat and guinea pig (Gordon et al, 1978) as well as marmoset and rhesus monkey (Dimhuber et al, 1979). Thus, due to the CarbE concept, we were fairly convinced that the hiunan species would achieve a similar protection by pyridostigmine prophylaxis as rhesus monkey, since both species lack the... 

FIGURE 68.2. Visual representation of soman LD50 in rat as proportionally influenced by 1. target AChE, 2. plasma CarbE, 3. carbamate prophylaxis, and 4. artificially supplied scavenger (at rat plasma CarbE concentration). The concentration of target AChE (1) or its enhancement by carbamate prophylaxis (3) is constant between the species, whereas the concentration of plasma CarbE (2) is varying. The representation is based on the CarbE concept outlined by Sterri and Fonnum (1989) and Sterri (1989). LD50 decreases (toxicity increases) when plasma CarbE (2) is decreased or absent. 

Immunosuppressant IMPDH carbamate prodrug, (VII), illustrated in Eq. 2, prepared by Stamos (8) were used in the treatment or prophylaxis of transplant rejection and autoimmune disorders. 

Intact AChE is a basic requirement for normal function of the organism and thus for effective prophylaxis. The enzyme is changed in a way that will make it resistant to OP. This can be achieved by using reversible inhibitors (preferably carbamates), which are able to inhibit AChE reversibly, and after spontaneous recovery of the activity (decarbamylation) normal AChE serves as a source of an active enzyme. 

Tonkopii, V. (2003). Stmcture and efficiency of carbamates as drugs for prophylaxis against OP poisoning. In Symposium Proceedings, NBC 2003 (K. Laihia, ed.), pp. 140-1. Jyvaskyla. 

Tonkopii, V., Structure and efficiency of carbamates as drugs for prophylaxis against OP poisoning,... 

In the case of soman, therefore, once ageing has occurred, recovery of enzyme function depends on re-synthesis of AChE. As a result, it is important that an oxime is administered as soon after soman exposure as possible so that some reactivation of AChE occurs before all of the enzyme becomes aged. The phenomenon of soman-induced ageing led to the development of carbamate (pyridostigmine) prophylaxis for nerve agent poisoning. 

Karlsson, N., Larsson, R., and Pun, G., Ferrocene-carbamate as prophylaxis against soman poisoning. Fund. Appl Toxicol, 4, S184, 1984. 

---