Methods for prevention and treatment of convulsive disorders associated with сholinergic convulsant intoxication

Abstract

Organophosphates (OPs) and carbamates are a common cause of intoxication associated with convulsive disorders. These cholinergic substances form a bond with acetylcholinesterase (AChE), thus contributing to accumulation of acetylcholine in synapses and causing typical manifestations of toxicity, including seizures. Standard antidote therapy provides sufficient symptom control, reduces seizures and decreases mortality only in case of prescription at the early stage of poisoning or preventive administration. Traditionally, atropine is used, that blocks the activity of the muscarinic cholinergic receptors in the parasympathetic nervous system and reduce the smooth muscle contraction activity, along with oximes that reactivate the reversibly inhibited AChE in the nicotinic acetylcholine receptors found in skeletal muscle. If these are not sufficient, benzodiazepines that interact with γ-aminobutyric acid receptors are used to jugulate seizures, prevent organic brain desease and post-traumatic epilepsy. There are no unified guidelines for the cases of antidotes having no effect or insufficient efficacy of antidotes. Unwanted side effects of the existing drugs and progressive decrease of efficiency within 30 min after exposure to OPs necessitate the search for new agents. Combination therapy, new dosage forms, developing original molecules or modifying the existing ones are among the developed approaches discussed in our review.