Histamine in brain--its role in regulation of seizure susceptibility.
The influence of drugs affecting the turnover and levels of histamine in brain and histamine antagonists on pentetrazole (PTZ)-induced and electroconvulsive seizure threshold in mice was studied. A 1.5-2-fold rise in histamine brain concentration (induced by treatment with histidine or metoprine), led to a concomitant increase of PTZ-induced seizure threshold. A histidine decarboxylase inhibitor (brocresine) induced a depletion of brain histamine by about 75% for at least 8 h, the seizure threshold was, however, only reduced at 6 and 8 h after the injection. At shorter intervals, the seizure threshold was substantially increased. Treatment with centrally acting H1 antagonists (dimethindene and promethazine) in non-sedative dosage diminished the PTZ seizure threshold significantly; no changes were seen after treatment with H2 and H3 antagonists (oxmetidine, ranitidine, zolantidine or thioperamide) and a H3 agonist (R-alpha-methylhistamine). The electroconvulsive threshold was hardly influenced. It is concluded that histamine has a certain anticonvulsant effect which is mediated through H1 receptors.
Scherkl
R
R
Department of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universität Berlin, Germany.
Hashem
A
A
Frey
H H
HH
D000818:Animals; D001921:Brain / Q000503:physiopathology*; D004198:Disease Susceptibility; D004597:Electroshock; D006632:Histamine / Q000502:physiology*; D006633:Histamine Antagonists / Q000494:pharmacology; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D010433:Pentylenetetrazole; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*
D006633:Histamine Antagonists; D008761:Methylhistamines; C069357:alpha-methylhistamine; D006632:Histamine; D010433:Pentylenetetrazole