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].
