Pharmacological effects of carcinine on histaminergic neurons in the brain

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 H-3 receptor over H-1 or H-2 receptor (K-i (muM) = 0.2939 +/- 0.2188 vs 3621.2 +/- 583.9 or 365.3 +/- 232.8 muM, 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 H-3 receptor antagonist, carcinine ( 20, 50 mM) 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 completedly reversed by (R)-alpha-methylhistamine, a representative H-3 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 H-3 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.