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Studies with a PNMT inhibitor
Author(s) -
Dubb J. W.,
Stote R. M.,
Alexander F.,
Intoccia A. P.,
Geczy M.,
Pendleton R. G.
Publication year - 1979
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1979256837
Subject(s) - phenylethanolamine , phenylethanolamine n methyltransferase , endocrinology , central nervous system , medicine , urinary system , pharmacology , urine , chemistry , dopamine , tyrosine hydroxylase
DCTQ (SK&F 64139) is a potent inhibitor of both adrenal and central nervous system (CNS) phenylethanolamine N‐methyltransferase (PNMT). In animal studies, a plasma level of 0.35 µg/ml was associated with 50% inhibition of both adrenal and central PNMT. We performed single‐dose phase I studies with DCTQ in man. Plasma drug levels up to 6.26 µg/ml were readily obtained. There were few subjective and no objective clinical changes. DCTQ did not alter blood pressure or cause CNS symptoms in man. Furthermore, resting plasma and urinary catecholamines did not change after DCTQ. The study suggests that acute inhibition of PNMT under resting conditions is without significant clinical effect.