The metabolic fate of the dopamine agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin in rats after intravenous and oral administration. II. Isolation and identification of metabolites.
1. The in vivo metabolic pathways of 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (I) in rats have been established, using in vitro metabolism as a complementary technique. 2. All identified metabolites were conjugates. Glucuronidation at the phenolic group yields the major metabolite, accounting for 50% (i.v.) or 65% (oral) of the dose. The corresponding sulphate conjugate of I is virtually absent (less than 0.2% dose). 3. Hydroxylation of I, at the ortho position to the phenolic hydroxy group, yields 6-hydroxy-I (II), accounting for about 13% (i.v.) or 9% (oral) dose. This catechol is excreted, as a glucuronide, almost exclusively into the bile. Both the 5- and the 6-glucuronide of II were detected in about equal amounts. 4. Metabolism of I in vitro showed that under oxidative conditions, depropylation of I occurred. Conjugation of 3H-I in the presence of UDPGA or PAPS, was successful in yielding the glucuronide and sulphate conjugates.
Gerding
T K
TK
Department of Toxicology, State University, Groningen, The Netherlands.
Drenth
B F
BF
de Zeeuw
R A
RA
Tepper
P G
PG
Horn
A S
AS
D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D015259:Dopamine Agents / Q000378:metabolism*; D005965:Glucuronates / Q000378:metabolism; D006900:Hydroxylation; D007262:Infusions, Intravenous; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D015394:Molecular Structure; D009281:Naphthalenes / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013431:Sulfates / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000378:metabolism*; D013876:Thiophenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000378:metabolism*
D015259:Dopamine Agents; D005965:Glucuronates; D009281:Naphthalenes; D013431:Sulfates; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine