Safety

Hazardous Substances Data

7187-66-8(Hazardous Substances Data)

Hazard and Precautionary Statements (GHS)

Trimethaphan Chemical Properties,Usage,Production

Uses

Trimethaphan is used for the controlled reduction in blood pressure during surgical interventions, for quick regulation during sharp increases in blood pressure, immediate interventions during pulmonary edema, ischemic illnesses of the heart, and in cases where other drugs cannot be used.

Definition

ChEBI: A complex heterocyclic sulfonium compound with an imidazolium core, used to treat hypertension.

Clinical Use

Trimethaphan camsylate (Arfonad) is an extremely short-acting agent whose major therapeutic use is in the production of controlled hypotension in certain surgical procedures and in the emergency treatment of hypertensive crisis. Continuous infusion may be employed to maintain its antihypertensive effect, especially in patients with an acute dissecting aortic aneurysm. Much of the decrease in blood pressure following trimethaphan administration is thought to be due to its direct vasodilating properties.
Trimethaphan can produce prolonged neuromuscular blockade in some patients, and therefore, it should be used with caution as a hypotensive agent during surgery. It also has been reported to potentiate the neuromuscular blocking action of tubocurarine, and because of its histamine-releasing properties, trimethaphan should be used with caution in patients with allergies.

Synthesis

Trimethaphan, D-3,4-(1,3-dibenzyl-2-oxoimidazolidino)-1,2-trimethylenthiophanium D-camphorsulfonate (14.2.12), is an intermediate product of biotin (vitamin H) synthesis. It is synthesized from fumaric acid, the bromination of which leads to meso-dibromosuccinic acid (14.2.3). Reacting this with benzylamine gives 2,3-bis-(benzylamino)succinic acid (14.2.4), which when treated with phosgene gives 1,3-dibenzyl-2- oxoimidazolidin-4,5-dicarboxylic acid (14.2.5). Dehydration of this product produces the corresponding imidazoline derivative of succinic acid (14.2.6). Reduction of this using zinc in acetic acid and subsequent treatment with hydrogen sulfide gives 1,3-dibenzyl-2,5- dioxotetrahydrothieno[3,4]imidazoline (14.2.7), which is reacted with 3-ethoxypropylmagnesiumbromide. The resulting carbinol (14.2.8) undergoes acidic dehydration to (14.2.9) and is further reduced (having formed a double bond) by hydrogen using Raney nickel as a catalyst. Cleavage of the ester bond in the resulting product (14.2.10) with the help of hydrogen bromide in acetic acid gives 3,4-(1,3-dibenzyl-2-oxoimidazolidino)-1,2- trimethylenthiophanium bromide (14.2.11), the treatment of which with silver D-camphorsulfonate gives trimethaphan (14.2.12) [34-38].