1st generation anticoagulants

All anticoagulant rodenticides have the same mode of action, i.e. interference with the synthesis of clotting factors, which results in haemorrhaging and death. In the liver cells, the biologically inactive vitamin K1-2,3 epoxide is reduced by a microsomal enzyme into biologically active vitamin K, which is essential for the synthesis of prothrombin and other clotting factors. Anticoagulant rodenticides antagonize the enzyme vitamin K1-epoxide reductase in the liver causing a gradual depletion of the vitamin and consequently of vitamin K-dependent clotting factors. This results in an increase in blood-clotting time until the point where the clotting mechanism fails. The principal use of anticoagulants worldwide has been for control of commensal rodents, primarily Norway rats, ship rats, and house mice. About ten anticoagulant rodenticides have been brought to the market. Some are reviewed here to illustrate their properties. A number have been registered for commensal rodent control.

The first-generation anticoagulants came into use during the early 1950s and revolutionised rodent control with outstanding safety and efficacy. The second-generation anticoagulants were introduced to overcome resistance to the first-generation compounds, which was first observed in the late 1950s.

Warfarin, is the earliest first-generation anticoagulant rodenticide. It has been used in a range of rodent baits since it was first introduced in 1947. Warfarin, like the other anticoagulants, inhibits the synthesis of vitamin K-dependent clotting factors. Symptoms of poisoning do not appear suddenly, and will culminate in death in rats within about 5–7 days of initial ingestion. The single dose LD50 is 50–100mg/kg in rats versus daily doses of 1 mg/kg for 5 days which will kill rats in 5–8 days.

Chlorophacinone and Diphacinone are anticoagulants, of the indane-dione class, which differs chemically from hydroxycoumarin anticoagulants such as warfarin or brodifacoum. Diphacinone is more toxic than warfarin to most species of rats and mice. Clinical and post-mortem signs of toxicosis are as for other anticoagulants. The persistence of diphacinone in the liver is similar to other first-generation anticoagulants which are rapidly eliminated and do not bio-accumulate like the second-generation anticoagulants. Chlorophacinone has similar properties to diphacinone but with slightly greater potency.

Coumatetralyl was launched in 1957, and is marketed worldwide and is more potent than warfarin and some other first-generation compounds. It is used as a tracking powder or as a cereal bait, wax block or paste for rodent control. Like other anticoagulant rodenticides, coumatetralyl inhibits the formation of vitamin K-dependent clotting factors. It is less persistent (in sub-lethally poisoned animals) than brodifacoum, but more persistent than diphacinone, and will have similar humaneness to other anticoagulant rodenticides.