Can Galantamine Act as an Antidote for Organophosphate Poisoning? A Review

Abstract

Indu, et al.: Galantamine in the Management of Organophosphate PoisoningOrganophosphate compounds are commonly used as insecticides in rural areas and powerful warfare agents by military personnel. These agents inhibit cholinesterases especially acetylcholinesterase and accumulate acetylcholine causing muscarinic, nicotinic and central nervous system manifestations. Currently, drugs such as atropine, oximes and benzodiazepine are used to treat these symptoms. But these drugs are associated with certain drawbacks and have found to be ineffective in preventing the delayed symptoms. This review analyses the rationalities in considering galantamine as an effective choice in the management of organophosphate toxicity. The mechanism is based on reversible competitive inhibiting property of galantamine on acetylcholinesterase without affecting butylcholinesterase. The drug can prevent the delayed cognitive effects and neurodegeneration by acting as a nicotinic allosteric potentiating ligand. It can cross the blood brain barrier and reversibly inhibit acetylcholinesterase in the brain and decrease the incidence of central nervous system manifestations such as convulsions. The drug is associated with good pharmacokinetic profile, minimal side effects and has been found to be effective as a pretreatment and post treatment agent. Thus, galantamine can be considered as an effective therapeutic agent in management of organophosphate toxicity.Key words: Acetylcholinesterase, galantamine, organophosphate compound, poisoning management, therapeutic approachesOrganophosphate compounds are used as insecticides and powerful warfare agents worldwide. The differences in the properties are based on the substituents attached to the basic moiety. The highly toxic compounds were developed as warfare agents and lesser toxic agents as insecticidal agents [1,2] . Among the commonly used agrochemicals, organophosphates were found to be the most preferred one due to their wide spectrum bioactivity and easy availability [3] . Parathion, fenthion, malathion, diazinon, chlorpyrifos (Dursban), terbufos, acephate, phorate, methyl parathion, phosmet, azinphos-methyl and dimethoate are the commonly used insecticidal agents. World Health Organization (WHO) has described that these agents belong to the extremely hazardous category, yet no law or policies exist to restrict their availability to the public [4][5][6] . Organophosphate compounds are responsible for large scale accidental poisoning and suicidal poisoning in developed countries [7] . Compounds such as soman (1,2,2-trimethyl propylmethyl phosphono fluoridate), sarin (isopropyl methyl phosphono fluoridate), tabun (ethyl dimethyl phosphoramidocyanidate) and VX (ethyl-S-diisopropylamino ethyl methyl phosphono thioate) are used as warfare agents, capable of causing mass destruction in war [8] . Thus, organophosphate poisoning became a major public health hazard to be therapeutically managed effectively. MECHANISM OF ACTION AND CLINICAL SYMPTOMSOrganophosphate compounds may enter into the human ...

A complete, evidence-based review on novichok poisoning based on epidemiological aspects and clinical management

“…In some studies, Rivastigmine revealed high inter-patient variability because of its complex pharmacological profile ( Lavon et al, 2015 ; Park et al, 2018 ). Furthermore, Galantamine, based on some preclinical studies, seems to be potent and effective with low toxicity ( Indu et al, 2016 ). Other animal investigations have demonstrated the efficacy of drugs like as Galantamine, Physostigmine, Trihexyphenidyl, Benactyzine, and Procyclidine; however, in anticonvulsant doses against Soman, they all resulted in behavioral impairments ( Myhrer and Aas, 2016 ).…”

Atropine Induced Delirium in Organophosphate (OP) Insecticide Poisoning: A Case Report

“…This in turn would help in designing a better evidence-based therapy. 13 Recent evidence suggests the use of galantamine in OP poisoning cases. Galantamine is an irreversible competitive inhibitor of AChE and up lights the possible outcomes of galantine use in OP poisoning.…”

“…Furthermore, the property of Galantamine in the prevention of neurodegeneration is ideal for OP poisoning cases. 13 However, atropine and pralidoxime have been widely employed for intoxication. Atropine competitively antagonizes acetylcholine only at muscarinic receptors while being ineffective on the nicotinic receptors attributing to its inefficacy in the prevention of clinical manifestations involving muscle weakness, 14 respiratory depression, convulsion and coma where supportive care should be initiated.…”