debrisoquine

Originator

Declinax,Roche,UK,1967

The Uses of debrisoquine

Antihypertensive.

Background

An adrenergic neuron-blocking drug similar in effects to guanethidine. It is also noteworthy in being a substrate for a polymorphic cytochrome P-450 enzyme. Persons with certain isoforms of this enzyme are unable to properly metabolize this and many other clinically important drugs. They are commonly referred to as having a debrisoquin 4-hydroxylase polymorphism.

Indications

For the treatment of moderate and severe hypertension, either alone or as an adjunct, and for the treatment of renal hypertension.

Definition

ChEBI: Debrisoquin is a member of isoquinolines and a carboxamidine. It has a role as an antihypertensive agent, an adrenergic agent, a sympatholytic agent and a human metabolite.

Manufacturing Process

27 g of 1,2,3,4-tetrahydroisoquinoline was added at room temperature to a solution of 28 g of 2-methyl-2-isothiourea sulfate in 80 ml of water. The resulting mixture was kept at room temperature with occasional shaking. After a short period of time, methylmercaptan began to escape, and the mixture warmed up slightly. After then standing for 24 hours, crystals formed. They were filtered off and rinsed with ice cold water. Recrystallization from approximately 100 ml of water yielded 1,2,3,4-tetrahydroisoquinoline-2- carboxamidine sulfate melting at 278°C to 280°C (uncorr.).
Another batch prepared in the same manner melted at 284°C to 285°C due to a minute difference in moisture content.
Both batches prepared above analyzed correctly for (C10H13N3)2·H2SO4.

brand name

Declinax (HoffmannLaRoche).

Therapeutic Function

Antihypertensive

Pharmacokinetics

Debrisoquin is an adrenergic neuron-blocking drug similar in effects to guanethidine. It is a substrate for a polymorphic cytochrome P-450 enzyme. Persons with certain isoforms of this enzyme are unable to properly metabolize this and many other clinically important drugs. They are commonly referred to as having a debrisoquin 4-hydroxylase polymorphism.

Metabolism

Hepatic.