Mehanizam toksičnog djelovanja karbamata

The toxic effects of carbamates to animals are due to the fact that these compounds inhibit acetylcholinesterase. Unlike some of the organophosphate insecticides (see Chapter 18), they do so without the need for undergoing a prior biotransformation and are therefore classified as direct inhibitors. Their inhibition of acetylcholinesterase is relatively reversible. Loss of acetylcholinesterase inhibition activity may result from hydrolysis of the carbamate ester, which can occur metabolically. In general, carbamates have a wide range between a dose that causes onset of poisoning symptoms and a fatal dose (see discussion of dose–response in Section 6.5). Although pirimicarb has a high systemic mammalian toxicity, its effects are mitigated by its low tendency to be absorbed through the skin.

Acetylcholine is a neurotransmitter, a key substance involved with transmission of nerve impulses in the brain, skeletal muscles, and other areas where nerve impulses occur. An essential step in the proper function of any nerve impulse is its cessation (see Figure 6.9), which requires hydrolysis of acetylcholine as shown by Reaction 6.10.1. Some xenobiotics, such as organophosphate compounds (see Chapter 18) and carbamates (see Chapter 15) inhibit acetylcholinesterase, with the result that acetylcholine accumulates and nerves are overstimulated. (Toxicological chemistry and biochemistry, 3rd edition, S. E. Manahan)

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