Effects of clonidine in a primed rat model of acute hepatic porphyria.
Acute hepatic porphyrias can be induced by several drugs and acute attacks of porphyrias are often associated with severe hypertension. Therefore it is important to know if an antihypertensive drug used has porphyrogenic potency or not. As previously demonstrated in normal rats the alpha-receptor blocker clonidine (CAS 4205-90-7) has no significant influence on the porphyrin metabolism. Pretreatment of rats with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) or allyl-isopropyl-acetamide (AIA) induces hepatic delta-aminolaevulinic acid synthase (ALA-S) and increases the urinary excretion of porphyrin precursors (ALA and PBG) comparable to the latent phase of acute hepatic porphyrias in humans. Clonidine did not induce hepatic ALA-S or urinary excretion of ALA or PBG in normal as well as in DDC or AIA pretreated rats. Moreover the induction of P4501A1 (7-ethoxyresorufin-O-deethylase) by DDC was abolished by simultaneous application of clonidine. From these findings one can probably conclude that clonidine is a safe drug in human acute hepatic porphyria.
Goerz
G
G
Department of Dermatology, Heinrich-Heine-University, Düsseldorf, Germany.
Bolsen
K
K
Böhrer
H
H
Fritsch
C
C
Kalka
K
K
Rominger
K L
KL
D000624:5-Aminolevulinate Synthetase / Q000096:biosynthesis; D000502:Allylisopropylacetamide / Q000633:toxicity; D000622:Aminolevulinic Acid / Q000652:urine; D000633:Aminopyrine N-Demethylase / Q000096:biosynthesis; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D003997:Dicarbethoxydihydrocollidine / Q000633:toxicity; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007527:Isoenzymes / Q000096:biosynthesis; D011162:Porphobilinogen / Q000652:urine; D017118:Porphyria, Acute Intermittent / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism* / Q000652:urine; D051381:Rats
D000959:Antihypertensive Agents; D007527:Isoenzymes; D000502:Allylisopropylacetamide; D003997:Dicarbethoxydihydrocollidine; D011162:Porphobilinogen; D000622:Aminolevulinic Acid; D019363:Cytochrome P-450 CYP1A1; D000633:Aminopyrine N-Demethylase; D000624:5-Aminolevulinate Synthetase; D003000:Clonidine