title: Potential pharmacological strategies for the improved treatment of organophosphate-induced neurotoxicity.
abstract: Organophosphates (OP) are highly toxic compounds that cause cholinergic neuronal excitotoxicity and dysfunction by irreversible inhibition of acetylcholinesterase, resulting in delayed brain damage. This delayed secondary neuronal destruction, which arises primarily in the cholinergic areas of the brain that contain dense accumulations of cholinergic neurons and the majority of cholinergic projection, could be largely responsible for persistent profound neuropsychiatric and neurological impairments such as memory, cognitive, mental, emotional, motor, and sensory deficits in the victims of OP poisoning. The therapeutic strategies for reducing neuronal brain damage must adopt a multifunctional approach to the various steps of brain deterioration: (i) standard treatment with atropine and related anticholinergic compounds; (ii) anti-excitotoxic therapies to prevent cerebral edema, blockage of calcium influx, inhibition of apoptosis, and allow for the control of seizure; (iii) neuroprotection by aid of antioxidants and N-methyl-d-aspartate (NMDA) antagonists (multifunctional drug therapy), to inhibit/limit the secondary neuronal damage; and (iv) therapies targeting chronic neuropsychiatric and neurological symptoms. These neuroprotective strategies may prevent secondary neuronal damage in both early and late stages of OP poisoning, and thus may be a beneficial approach to treating the neuropsychological and neuronal impairments resulting from OP toxicity.
authors.affiliation: a Department of Pharmacology, ISF College of Pharmacy, Moga 142001, Punjab, India.
authors.forename: Shamsherjit
authors.initials: S
authors.lastname: Kaur
authors.forename: Satinderpal
authors.initials: S
authors.lastname: Singh
authors.forename: Karan Singh
authors.initials: KS
authors.lastname: Chahal
authors.forename: Atish
authors.initials: A
authors.lastname: Prakash
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001285:Atropine / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D018680:Cholinergic Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D059329:Cholinergic Neurons / Q000187:drug effects* / Q000473:pathology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D010755:Organophosphates / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D010755:Organophosphates; D001285:Atropine; D000110:Acetylcholinesterase
keywords: acetylcholinesterase; acétycholinestérase; cholinergic neuronal excitotoxicity; dommage neuronal secondaire; excitotoxicité neuronale cholinergique; neuroprotective strategies; organophosphates; organophosphorés; secondary neuronal damage; stratégies neuroprotectrices