Biomaterial Database

Competitive inhibition of sparteine oxidation in human liver by beta-adrenoceptor antagonists and other cardiovascular drugs. 1984

S V Otton, and T Inaba, and W Kalow

The rate of oxidation of sparteine by the 9000 x g supernatant fraction of a human liver was measured in the presence of various drugs which exert cardiovascular effects. Hexamethonium, ouabain, caffeine and isoproterenol had no effect on this rate, while alprenolol, metoprolol, oxprenolol, propranolol, timolol, pindolol, lidocaine, mexiletine, 17-n-pentyl-sparteine, tolazoline, quinine, quinidine, cinchonine and cinchonidine inhibited the in vitro reaction competitively. Stereoselective inhibition was observed between quinine (Ki = 15 microM) and quinidine (Ki = 0.06 microM). Genetic evidence suggests that the primary metabolism of sparteine depends on a single species of cytochrome P450. In vitro competitive inhibition of sparteine oxidation by a drug indicates that this drug is capable of occupying the same enzymatic site as sparteine. This may mean that the competing drug is also metabolized at that site and thereby subject to the same genetic variation as sparteine's oxidation; absence of inhibition excludes this possibility.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
D011802	Quinidine	An optical isomer of quinine, extracted from the bark of the CHINCHONA tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular ACTION POTENTIALS, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission.	Adaquin,Apo-Quinidine,Chinidin,Quincardine,Quinidex,Quinidine Sulfate,Quinora,Apo Quinidine,Sulfate, Quinidine
D011803	Quinine	An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood.	Biquinate,Legatrim,Myoquin,Quinamm,Quinbisan,Quinbisul,Quindan,Quinimax,Quinine Bisulfate,Quinine Hydrochloride,Quinine Lafran,Quinine Sulfate,Quinine Sulphate,Quinine-Odan,Quinoctal,Quinson,Quinsul,Strema,Surquina,Bisulfate, Quinine,Hydrochloride, Quinine,Sulfate, Quinine,Sulphate, Quinine
D002317	Cardiovascular Agents	Agents that affect the rate or intensity of cardiac contraction, blood vessel diameter, or blood volume.	Cardioactive Agent,Cardioactive Drug,Cardiovascular Agent,Cardiovascular Drug,Cardioactive Agents,Cardioactive Drugs,Cardiovascular Drugs,Agent, Cardioactive,Agent, Cardiovascular,Drug, Cardioactive,Drug, Cardiovascular
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000318	Adrenergic beta-Agonists	Drugs that selectively bind to and activate beta-adrenergic receptors.	Adrenergic beta-Receptor Agonists,beta-Adrenergic Agonists,beta-Adrenergic Receptor Agonists,Adrenergic beta-Agonist,Adrenergic beta-Receptor Agonist,Betamimetics,Receptor Agonists, beta-Adrenergic,Receptors Agonists, Adrenergic beta,beta-Adrenergic Agonist,beta-Adrenergic Receptor Agonist,Adrenergic beta Agonist,Adrenergic beta Agonists,Adrenergic beta Receptor Agonist,Adrenergic beta Receptor Agonists,Agonist, Adrenergic beta-Receptor,Agonist, beta-Adrenergic,Agonist, beta-Adrenergic Receptor,Agonists, Adrenergic beta-Receptor,Agonists, beta-Adrenergic,Agonists, beta-Adrenergic Receptor,Receptor Agonist, beta-Adrenergic,Receptor Agonists, beta Adrenergic,beta Adrenergic Agonist,beta Adrenergic Agonists,beta Adrenergic Receptor Agonist,beta Adrenergic Receptor Agonists,beta-Agonist, Adrenergic,beta-Agonists, Adrenergic,beta-Receptor Agonist, Adrenergic,beta-Receptor Agonists, Adrenergic
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