PRO-2-PAM: The First Therapeutic Drug for Reactivation of Organo-Phosphate-Inhibited Central (Brain) and Peripheral Cholinesterases
Abstract
Due to the documented use of organophosphorus (OP) chemical agents in warfare and by terrorists around the globe, Federal, State, and local authorities need novel therapeutics to overcome their deleterious effects. OPs inhibit cholinesterases (ChE), leading to accumulation of the neurotransmitter acetylcholine (ACh). Potentially lethal effects begin with secretion, muscle fasciculation, and paralysis in the peripheral nervous system (PNS). Central nervous system (CNS) perturbations include epileptic seizures leading to neuronal damage and long-term structural changes. Therapy for OP exposure is a combination of atropine sulfate to block the overload of cholinergic (muscarinic) receptors, the FDA approved cholinesterase reactivator (oxime) pralidoxime chloride (2-PAM), and a benzodiazepine (diazepam) anticonvulsant to ameliorate seizures. However, current therapies for acute pesticide or organophosphate poisoning do not provide treatment for centrally inhibited cholinesterases because quaternary nitrogen charged oximes, including 2- PAM, do not cross the blood brain barrier.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2008
- Accession Number
- ADA505755
Entities
People
- Amy J. Campbell
- Angela R. Davis
- Elizabeth Marek
- Farhat A. Khan
- James C. Demar
- Latoya A. Hyson
- Madhusoodana P. Nambiar
- Richard K. Gordon
- Roberta R. Owens
- Ruthie H. Ratchiffe
Organizations
- Walter Reed Army Institute of Research