Interactions of apomorphine with serum and tissue proteins
Physical and covalent interactions of apomorphine with serum and tissue proteins could influence the drug's disposition and pharmacological activities in mammals. Ultrafiltration, equilibrium dialysis, and ultraviolet spectrophotometric methods have been used to study the reversible binding of apomorphine to bovine, human, rat, and swine plasma proteins. The degree of binding was generally greater than 90%, but variations were noted in some instances on the basis of drug concentrations and pH over the range of 6.8-7.8. Incubation of (8,9-/sup 3/H2)apomorphine with bovine serum albumin led to retention of radioactivity and a stoichiometrically controlled released of tritium which arose from the reaction of an electrophilic drug oxidation product and protein, producing drug-protein conjugates. In vitro experiments with mouse striatal brain preparations indicated parallel covalent binding reactions. In vivo experiments in mice indicated accumulation of radioactivity in brain regions and other tissues following daily injections of (8,9-/sup 3/H2)apomorphine for 14 days. The physical and covalent interactions of apomorphine with mammalian tissue proteins could be the cause of longer disposition half-lives in mammals than those previously reported. The covalent interactions, in particular, may be important in elucidating the mechanism of apomorphine-induced behavioral effects in mice.
- Research Organization:
- Univ. of Texas, Austin
- OSTI ID:
- 5098246
- Journal Information:
- J. Med. Chem.; (United States), Vol. 5
- Country of Publication:
- United States
- Language:
- English
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NARCOTICS
CONFIGURATION INTERACTION
PHARMACOLOGY
PROTEINS
TRITIUM COMPOUNDS
ALKALOIDS
ANALGESICS
BLOOD SERUM
DIALYSIS
IN VITRO
MICE
RATS
SPECTROPHOTOMETRY
SWINE
ULTRAFILTRATION
ANIMALS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DOMESTIC ANIMALS
DRUGS
FILTRATION
LABELLED COMPOUNDS
MAMMALS
ORGANIC COMPOUNDS
RODENTS
SEPARATION PROCESSES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques