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Dynamics of histamine H(3) receptor antagonists on brain histamine metabolism: do all histamine H(3) receptor antagonists act at a single site?
Eur J Pharmacol. 2001 Nov 16; 431(2):215-21.EJ

Abstract

Thioperamide, the prototypical histamine H(3) receptor antagonist, acts at the brain histamine H(3) autoreceptor to promote the release and metabolism of neuronal histamine, resulting in higher brain levels of the metabolite tele-methylhistamine. However, unlike thioperamide, several new histamine H(3) receptor antagonists enter the central nervous system (CNS), block brain histamine H(3) receptors and increase histamine release without increasing brain tele-methylhistamine levels. Experiments were performed presently in an attempt to understand these results. Consistent with previous findings, thioperamide significantly increased the content and synthesis rate of tele-methylhistamine in mouse and rat brain. In contrast, the histamine H(3) receptor antagonists GT-2227 (4-(6-cyclohexylhex-cis-3-enyl)imidazole) and clobenpropit did not affect tele-methylhistamine synthesis rate in mouse whole brain. The histamine H(3) receptor ligand GT-2016 (5-cyclohexyl-1-(4-imidazol-4-ylpiperidyl)pentan-1-one) had no effect on tele-methylhistamine levels in any rat brain region and decreased tele-methylhistamine synthesis rates in the mouse whole brain. To examine the possibility that these histamine H(3) receptor antagonists might prevent the methylation of newly released histamine, they were co-administered with thioperamide to determine their effects on the thioperamide-induced stimulation of tele-methylhistamine synthesis. GT-2016 significantly reduced the thioperamide-induced activation of tele-methylhistamine synthesis in mouse whole brain and in several regions of rat brain. Although further clarification is needed, these results suggest that some histamine H(3) receptor antagonists may promote the release of neuronal histamine, but also act to reduce histamine methylation in vivo by an unknown mechanism.

Authors+Show Affiliations

Neuropharmacology and Neuroscience, Albany Medical College, MC-136, 47 New Scotland Ave., Albany, NY 12208, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11728428

Citation

Barnes, W, et al. "Dynamics of Histamine H(3) Receptor Antagonists On Brain Histamine Metabolism: Do All Histamine H(3) Receptor Antagonists Act at a Single Site?" European Journal of Pharmacology, vol. 431, no. 2, 2001, pp. 215-21.
Barnes W, Boyd D, Hough L. Dynamics of histamine H(3) receptor antagonists on brain histamine metabolism: do all histamine H(3) receptor antagonists act at a single site? Eur J Pharmacol. 2001;431(2):215-21.
Barnes, W., Boyd, D., & Hough, L. (2001). Dynamics of histamine H(3) receptor antagonists on brain histamine metabolism: do all histamine H(3) receptor antagonists act at a single site? European Journal of Pharmacology, 431(2), 215-21.
Barnes W, Boyd D, Hough L. Dynamics of Histamine H(3) Receptor Antagonists On Brain Histamine Metabolism: Do All Histamine H(3) Receptor Antagonists Act at a Single Site. Eur J Pharmacol. 2001 Nov 16;431(2):215-21. PubMed PMID: 11728428.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dynamics of histamine H(3) receptor antagonists on brain histamine metabolism: do all histamine H(3) receptor antagonists act at a single site? AU - Barnes,W, AU - Boyd,D, AU - Hough,L, PY - 2001/12/1/pubmed PY - 2002/1/10/medline PY - 2001/12/1/entrez SP - 215 EP - 21 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 431 IS - 2 N2 - Thioperamide, the prototypical histamine H(3) receptor antagonist, acts at the brain histamine H(3) autoreceptor to promote the release and metabolism of neuronal histamine, resulting in higher brain levels of the metabolite tele-methylhistamine. However, unlike thioperamide, several new histamine H(3) receptor antagonists enter the central nervous system (CNS), block brain histamine H(3) receptors and increase histamine release without increasing brain tele-methylhistamine levels. Experiments were performed presently in an attempt to understand these results. Consistent with previous findings, thioperamide significantly increased the content and synthesis rate of tele-methylhistamine in mouse and rat brain. In contrast, the histamine H(3) receptor antagonists GT-2227 (4-(6-cyclohexylhex-cis-3-enyl)imidazole) and clobenpropit did not affect tele-methylhistamine synthesis rate in mouse whole brain. The histamine H(3) receptor ligand GT-2016 (5-cyclohexyl-1-(4-imidazol-4-ylpiperidyl)pentan-1-one) had no effect on tele-methylhistamine levels in any rat brain region and decreased tele-methylhistamine synthesis rates in the mouse whole brain. To examine the possibility that these histamine H(3) receptor antagonists might prevent the methylation of newly released histamine, they were co-administered with thioperamide to determine their effects on the thioperamide-induced stimulation of tele-methylhistamine synthesis. GT-2016 significantly reduced the thioperamide-induced activation of tele-methylhistamine synthesis in mouse whole brain and in several regions of rat brain. Although further clarification is needed, these results suggest that some histamine H(3) receptor antagonists may promote the release of neuronal histamine, but also act to reduce histamine methylation in vivo by an unknown mechanism. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/11728428/Dynamics_of_histamine_H_3__receptor_antagonists_on_brain_histamine_metabolism:_do_all_histamine_H_3__receptor_antagonists_act_at_a_single_site L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(01)01453-4 DB - PRIME DP - Unbound Medicine ER -