Effects of (S)-alpha-fluoromethylhistidine and (R)-alpha-methylhistamine on locomotion of W/Wv mice.
We studied the effects of inactivators of the central histaminergic neuron system, (R)-alpha-methylhistamine, a histamine H3 receptor agonist, and (S)-alpha-fluoromethylhistidine, a histamine synthesis inhibitor, on locomotor activity and brain histamine content of mast cell-deficient W/Wv mice using a recently developed high-performance liquid chromatography system coupled with a fluorometric detector. IP injection of (R)-alpha-methylhistamine (6-50 mg/kg) increased brain histamine content after 1 h but caused no significant change in locomotor activity. IP injection of (S)-alpha-fluoromethylhistidine decreased brain histamine content at doses of 6-50 mg/kg and locomotor activity at doses of 12.5-50 mg/kg. However, locomotor activity was decreased significantly (in Student's t-test) by sequential administrations of (S)-alpha-fluoromethylhistidine (6 mg/kg) and (R)-alpha-methylhistamine (12.5 or 25 mg/kg), but not by (S)-alpha-fluoromethylhistidine (6 mg/kg) and other doses of (R)-alpha-methylhistamine (6 or 50 mg/kg). These results support the hypothesis that the central histaminergic neuron system is involved in the control of spontaneous locomotion or alertness.
Sakai
N
N
Department of Pharmacology 1, Tohoku University School of Medicine, Sendai, Japan.
Yamazaki
S
S
Onodera
K
K
Yanai
K
K
Maeyama
K
K
Watanabe
T
T
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D006632:Histamine / Q000378:metabolism; D017442:Histamine Agonists / Q000494:pharmacology*; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology*; D008762:Methylhistidines / Q000494:pharmacology*; D051379:Mice; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000187:drug effects*; D018100:Receptors, Histamine H3 / Q000187:drug effects*; D013050:Spectrometry, Fluorescence
D017442:Histamine Agonists; D008761:Methylhistamines; D008762:Methylhistidines; D018100:Receptors, Histamine H3; C069357:alpha-methylhistamine; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D006640:Histidine Decarboxylase