Pharmacology of α fluoromethylhistidine, a specific inhibitor of histidine decarboxylase

doi:10.1016/0165-6147(90)90181-7

Trends in Pharmacological Sciences

Volume 11, Issue 9, September 1990, Pages 363-367

https://doi.org/10.1016/0165-6147(90)90181-7 Get rights and content

Abstract

α-Fluoromethyl-[S]-liistidine (FMH) is a specific and potent inhibitor of histidine decarboxylase, which forms histamine from histidine. It acts selectively and irreversibly by formation of a covalent linkage, possibly with the serine residue in the active site of the enzyme. A single administration of FMH decreases the histamine content only of non-mast cells in the brain and stomach of rodents, but repeated administration gradually decreases the histamine content of mast cells in all tissues. Thus, FMH can be used to deplete histamine in pharmacological studies. As no marked side-effects have been observed during administration of FMH, it may be useful in pathological conditions, such as some allergic diseases, peptic ulcers and mastocytosis, in which excess production of histamine is involved.

References (34)

L.B. Hough
Prog. Neurobiol.
(1988)
H. Kubota et al.
Biochem. Pharmacol.
(1984)
D.E. Duggan et al.
Biochem. Pharmacol.
(1984)
H. Hayashi et al.
J. Biol. Chem.
(1986)
K. Maeyama et al.
Biochem. Pharmacol.
(1982)
L.B. Hough et al.
Brain Res.
(1984)
J. Bartholeyns et al.
Contraception
(1982)
T.A. Slotkin et al.
Life Sci.
(1983)
S. Kiyono
Physiol. Behav.
(1985)
J-S. Lin et al.
Neuropharmacology
(1988)

M. Garbarg et al.

J. Eur. Pharmacol.

(1989)

M. Bouclier et al.

Eur. J. Pharmacol.

(1983)

V.S. Westerberg et al.

Pharmacol. Biochem. Behav.

(1987)

S. Hosoda et al.

Biochem. Pharmacol.

(1985)

J. Bartholeyns et al.

Trends Pharmacol. Sci.

(1985)

A.S. Tung

Biochem. Pharmacol.

(1985)

T.F. August

J. Pharm. Sci.

(1985)

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Citation Excerpt :
Next, we used FMH to clarify the importance of histamine release in the JNJ-induced increase in locomotor activity. FMH is a highly selective irreversible inhibitor of Hdc and does not affect other monoamine-related enzymes such as Hnmt, DOPA decarboxylase or glutamate decarboxylase even at high doses such as 100 mg/kg (Garbarg et al., 1980; Sakai et al., 1997; Watanabe et al., 1990). Thus, the nonspecific inhibition of FMH could be negligible.
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First, we examined the effect of JNJ injection to mice on the concentrations of brain monoamines and their metabolites. JNJ exclusively increased N^τ-methylhistamine, the metabolite of brain histamine used as an indicator of histamine release, suggesting that JNJ dominantly stimulates the release of histamine release but not of other monoamines.
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The histaminergic system in the central nervous system is involved in a large range of physiological, pathological and behavioral processes including the regulation of circadian rhythms, arousal, nutrition, thermoregulation, allergic responses, vestibular functions, inflammatory reactions, endocrine functions, pain perception, brain reward and reinforcement, exploratory behaviors, emotion, aggression and learning and memory (Dere et al., 2010; Haas and Panula, 2003; Schwartz et al., 1991; Watanabe et al., 1990).
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Trends in Pharmacological Sciences

TIPS reviewsPharmacology of α fluoromethylhistidine, a specific inhibitor of histidine decarboxylase

Abstract

Prog. Neurobiol.

Biochem. Pharmacol.

Biochem. Pharmacol.

J. Biol. Chem.

Biochem. Pharmacol.

Brain Res.

Contraception

Life Sci.

Physiol. Behav.

Neuropharmacology

J. Eur. Pharmacol.

Eur. J. Pharmacol.

Pharmacol. Biochem. Behav.

Biochem. Pharmacol.

Trends Pharmacol. Sci.

Biochem. Pharmacol.

J. Pharm. Sci.

TIPS reviews
Pharmacology of α fluoromethylhistidine, a specific inhibitor of histidine decarboxylase