Document Detail

S-[2-(4-imidazolyl)ethyl]isothiourea, a highly specific and potent histamine H3 receptor agonist.
MedLine Citation:
PMID:  1383495     Owner:  NLM     Status:  MEDLINE    
The effects of a new agonist of histamine (HA) H3 receptors, Imetit (S-[2-(4-(imidazolyl)ethyl]isothiourea) were investigated in vitro and in vivo and compared to those of (R)-alpha-methylhistamine [(R)-alpha-MeHA], a prototypic drug. Imetit inhibited the binding of [3H](R-alpha-MeHA to rat brain membranes with a Ki value of 0.1 +/- 0.01 nM. The release of endogenously synthesized [3H]HA induced by K(+)-depolarization from rat brain slices and synaptosomes was inhibited by Imetit with EC50 values of 1.0 +/- 0.3 and 2.8 +/- 0.7 nM, respectively. Imetit behaved as a full agonist and was about 4 times more potent than (R)-alpha-MeHA and 60 times more potent than HA. Thioperamide, a selective H3 receptor antagonist, elicited a parallel rightward shift of the concentration-response curve for Imetit with an apparent Ki value of 5.6 +/- 1.4 nM. Imetit potencies relative to HA were less than 0.1% and only 0.6% at HA H1 and H2 receptor reference systems, respectively. Imetit was found not to be a substrate or an inhibitor of HMT. After p.o. administration to mice or rats, Imetit decreased (by approximately 50%) the tele-MeHA level in the cerebral cortex with ED50 values of 1.0 +/- 0.3 and 1.6 +/- 0.3 mg/kg, respectively. This effect was still maximal after 6 hr. The in vivo potency and duration of action of Imetit were in the same range as those of (R)-alpha-MeHA. It is therefore concluded that Imetit represents a new potent and selective HA H3 receptor agonist.
M Garbarg; J M Arrang; A Rouleau; X Ligneau; M D Tuong; J C Schwartz; C R Ganellin
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  263     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1992 Oct 
Date Detail:
Created Date:  1992-11-20     Completed Date:  1992-11-20     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  304-10     Citation Subset:  IM    
Unité de Neurobiologie et Pharmacologie (U. 109), Institut National de la Santé et de la Recherche Médicale, Centre Paul Broca, Paris, France.
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MeSH Terms
Cerebral Cortex / drug effects*,  enzymology,  metabolism
Guinea Pigs
Histamine Agonists / pharmacology*
Histamine N-Methyltransferase / metabolism
Histamine Release / drug effects
Imidazoles / pharmacology*
Methylhistamines / metabolism
Receptors, Histamine / drug effects*
Receptors, Histamine H3
Thiourea / analogs & derivatives
Urea / analogs & derivatives*,  pharmacology
Reg. No./Substance:
0/Histamine Agonists; 0/Imidazoles; 0/Methylhistamines; 0/Receptors, Histamine; 0/Receptors, Histamine H3; 102203-18-9/imetit; 57-13-6/Urea; 62-56-6/Thiourea; EC N-Methyltransferase

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