Isoflurophate

The esters of monofluorophosphoric acid are of great interest because of their cholinesterase inhibiting activity which causes them to be highly toxic nerve gases and also gives them medical activity (see Enzyme inhibitors). The most studied is the bis(l-methylethyl)ester of phosphorofluoridic acid also known as diisopropyl phosphorofluoridate [155-91 DFP (5), and as the ophthalmic ointment or solution Isoflurophate USP. It is used as a... 

Acetazolamide Bucloxic acid Butalamine HCI Chlorotrianisene Chlorquinaldol Clenbuterol Diazoxide Enflurane Floxacillin Flucloronide Isoflurophate Lindane Methazolamide Metoclopramide HCI Oxacillin sodium Chloroacetaldehyde Benzthiazide... 

CiHgO 67-65-0) see Fenofibratc Imiquimod Isoflurophate Nimodipine isopropenyl acetate... 

CjHjoNOjPS 3147-20-4) see Ecothiopate iodide phosphorus trichloride (C1-,P 7719-12-2) see Isoflurophate phosphoryl chloride... 

Isoflurophate Isoflurophate, the di-wo-propyl ester of fluorophosphoric acid (13.2.21), is made by reacting Mo-propyl alcohol with phosphorous trichloride, forming di-wo-propy-Iphosphite (13.2.19), which is chlorinated to (13.2.20), and further reacted with sodium fluoride to replace the chlorine atom with fluorine, thus giving isofluorophate (13.2.21) [50]. 

Examples of X groups are fluorine in isoflurophate (Floropryl, no longer available in the United States or Canada) and echothiophate (Phospholine). Parathion and malathion (insecticides) are thiophosphates... 

In the interaction of isoflurophate with AChE, a phosphorylated intermediate is formed and fluoride is released. An important characteristic of the organophos-phate-induced inhibition is that the bond between the phosphate and the enzyme is very stable. While the regeneration of most carbamylated enzymes occurs with a half-life of minutes or hours, the recovery of a phosphorylated enzyme is generally measured in days. These agents are referred to, therefore, as irreversible inhibitors. 

Mechanism of action Isoflurophate [eye soe FLURE oh fate] (diisopropylfluorophosphate, DFP) is an organophosphate that covalently binds to a serine-OH at the active site of acetylcholinesterase (Figure 4.9). Once this occurs, the enzyme is permanently inactivated, and restoration of acetylcholinesterase activity requires the synthesis of new enzyme molecules. Following covalent modification of acetylcholinesterase, the phosphorylated enzyme slowly releases one of its isopropyl groups (Figure 4.9). The loss of an alkyl group, which is called... 

Actions Actions include generalized cholinergic stimulation, paralysis of motor function (causing breathing difficulties), and convulsions. Isoflurophate produces intense miosis and thus has found therapeutic use. Atropine in high dosage can reverse many of the muscarinic and central effects of isoflurophate. 

Therapeutic uses An ophthalmic ointment of the drug is used topically in the eye for the chronic treatment of open-angle glaucoma. The effects may last for up to one week after a single administration. [Note Echothiophate [ek oe THI oh fate] is a newer drug that covalently bonds to acetylcholinesterase. Its use is the same as isoflurophate.]... 

Covalent modification of acetylcholinesterase by isoflurophate also shown is the reactivation of the enzyme with pralidoxime. 

Which of the following is NOT an expected symptom of poisoning with isoflurophate ... 

Correct answer = O. Bradycardia (rather than tachycardia) and decreased cardiac output result from increased parasympathetic stimulation. Since isoflurophate inhibits acetylcholinesterase and increases the concentration of acetylcholine at the synapse, it mimics (parasympathetic) stimulation. 

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