Biomaterial Database

The genetic polymorphism of debrisoquine/sparteine metabolism--clinical aspects. 1990

M Eichelbaum, and A S Gross

Dr Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Stuttgart, F.R.G.

It has been established that the metabolism of more than twenty drugs, including antiarrhythmics, beta-adrenoceptor antagonists, antidepressants, opiates and neuroleptics is catalyzed by cytochrome P-450dbl. The activity of this P-450 isozyme is under genetic rather than environmental control. This article discusses the therapeutic implications for each of the classes of drugs affected by this genetic polymorphism in drug metabolism. Not only are the problems associated with poor metabolizers who are unable to metabolize the compounds discussed, but it is also emphasized that it is difficult to attain therapeutic plasma concentrations for some drugs in high activity extensive metabolizers.

UI	MeSH Term	Description	Entries
D007546	Isoquinolines	A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
D011110	Polymorphism, Genetic	The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.	Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D003647	Debrisoquin	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.	Debrisoquine,Tendor
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013034	Sparteine	A quinolizidine alkaloid isolated from several FABACEAE including LUPINUS; SPARTIUM; and CYTISUS. It has been used as an oxytocic and an anti-arrhythmia agent. It has also been of interest as an indicator of CYP2D6 genotype.	7,14-Methano-2H,6H-dipyrido(1,2-a:1',2'-e)(1,5)diazocine, dodecahydro-, (7S-(7alpha,7aalpha,14alpha,14abeta))-,Lupinidin,Lupinidine,Pachycarpine,D-sparteine,Depasan Retard,Genisteine Alkaloid,L-Sparteine,Pachycarpine Sulfate (1:1), Pentahydrate, (7S-(7alpha,7aalpha,14alpha,14abeta))-Isomer,Sparteine Hydrochloride, (7R-(7alpha,7aalpha,14alpha,14abeta))-Isomer,Sparteine Hydrochloride, (7S-(7alpha,7aalpha,14alpha,14abeta))-Isomer,Sparteine Hydroiodide, (7R-(7alpha,7aalpha,14alpha,14abeta))-Isomer,Sparteine Monohydrochloride, (7R-(7alpha,7aalpha,14alpha,14abeta))-Isomer,Sparteine Monohydroiodide, (7R-(7alpha,7aalpha,14alpha,14abeta))-Isomer,Sparteine Sulfate,Sparteine Sulfate (1:1), (7S-(7alpha,7aalpha,14alpha,14aalpha))-Isomer,Sparteine Sulfate (1:1), (7S-(7alpha,7aalpha,14alpha,14abeta))-Isomer,Sparteine Sulfate Anhydrous,Sparteine, (+)-Isomer,Sparteine, (-)-Isomer,Sparteine, (7R-(7alpha,7aalpha,14alpha,14abeta))-Isomer,Sparteine, (7R-(7alpha,7abeta,14alpha,14abeta))-Isomer,Sparteine, (7S-(7alpha,7aalpha,14alpha,14aalpha))-Isomer,Sparteine, (7S-(7alpha,7aalpha,14alpha,14abeta))-Isomer,Sparteine, (7S-(7alpha,7abeta,14alpha,14abeta))-Isomer,alpha-Isosparteine,beta-Isosparteine,Anhydrous, Sparteine Sulfate,Sulfate Anhydrous, Sparteine,alpha Isosparteine,beta Isosparteine