1
Carcinine (beta-alanyl
histamine) is an
imidazole dipeptide. The present study was designed to characterize the pharmacological effects of
carcinine on histaminergic activity in the brain and on certain neurobehavior. 2
Carcinine was highly selective for the
histamine H3 receptor over H1 or H2 receptor (Ki (microM)=0.2939+/-0.2188 vs 3621.2+/-583.9 or 365.3+/-232.8 microM, respectively). 3
Carcinine at a dose of 20 mg kg(-1) slightly increased
histidine decarboxylase (HDC) activity in the cortex (from 0.186+/-0.069 to 0.227+/-0.009 pmol mg
protein(-1) min(-1)). In addition,
carcinine (10, 20, and 50 mg kg(-1)) significantly decreased
histamine levels in mice brain. 4 Like
thioperamide, a
histamine H3 receptor antagonist,
carcinine (20, 50 microM) significantly increased
5-HT release from mice cortex slices, but had no apparent effect on
dopamine release. 5
Carcinine (20 mg kg(-1)) significantly inhibited
pentylenetetrazole-induced kindling. This inhibition was completely reversed by (R)-
alpha-methylhistamine, a representative
H3 receptor agonist, and alpha-fluromethylhistidine, a selective HDC inhibitor. 6
Carcinine (20 mg kg(-1)) ameliorated the learning deficit induced by
scopolamine. This amelioration was reversed by (R)-
alpha-methylhistamine as evaluated by the passive avoidance test in mice. 7 Like
thioperamide,
carcinine dose-dependently increased mice locomotor activity in the open-field test. 8 The results of this study provide first and direct evidence that
carcinine, as a novel
histamine H3 receptor antagonist, plays an important role in histaminergic neurons activation and might be useful in the treatment of certain diseases, such as
epilepsy, and locomotor or cognitive deficit.