Pharmacology, pharmacokinetics and metabolism of the dopamine receptor agonist 5-hydroxy-6-methyl-2-di-n-propylaminotetralin (DK-118) in the cat
The dopamine receptor agonist 5-hydroxy-6-methyl-2-di-n-propylaminotetralin (DK-118) lowers blood pressure, heart rat and inhibits tachycardia induced in cats by electrical stimulation of sympathetic nerves innervating the heart. DK-118, unlike most of its chemically related dopaminergic analogs, exhibits a slow onset of activity suggesting that one or more metabolites of the drug may be responsible for its pharmacologic effects. The purpose of the work described in this thesis was to gain information regarding the possible bioactivation of DK-118 in cats. In one series of experiments, cats were pretreated with inhibitors of drug metabolism, metyrapone or SKF 525-A, and alterations of the pharmacologic effects of DK-118 determined. A high-performance liquid chromatography assay-using electrochemical detection was developed to quantify urine and plasma concentrations of DK-118 in control, metyrapone pretreated and SKF 525-A pretreated cats. Urinary metabolites of (/sup 14/C)DK-118 were identified employing HPLC, GC/MS and FAB/MS. Pharmacologic activity and receptor binding of selected metabolites were determined. Data presented in this thesis are consistent with the hypothesis that metabolites contribute to some of the pharmacologic effects of DK-118.
- Research Organization:
- Iowa Univ., Iowa City (USA)
- OSTI ID:
- 6518317
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BLOOD
BLOOD PLASMA
BLOOD PRESSURE
BODY
BODY FLUIDS
BRAIN
CARBON 14 COMPOUNDS
CARDIOVASCULAR SYSTEM
CATS
CENTRAL NERVOUS SYSTEM
CHROMATOGRAPHY
DRUGS
HEART
KINETICS
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
MATERIALS
MEMBRANE PROTEINS
METABOLIC ACTIVATION
METABOLISM
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
PHARMACOLOGY
PROTEINS
REACTION KINETICS
RECEPTORS
SEPARATION PROCESSES
SYMPATHOLYTICS
URINE
VERTEBRATES
WASTES