Time course of the effects of histamine, thioperamide and EEDQ on H3 receptors in the mouse brain.

The effects of histamine, thioperamide and EEDQ (N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) at the noradrenaline release-modulating H3 receptor in the mouse brain were examined. In superfused mouse brain cortex slices preincubated with 3H-noradrenaline, the inhibitory effect of histamine on the electrically (0.3 Hz) evoked tritium overflow was virtually identical when the time of exposure was 30, 80 or 130 min; after withdrawal of histamine, the evoked overflow recovered within 80 min. The attenuation of the effect of histamine by thioperamide was reversible within 50 min after withdrawal of the antagonist, whereas the attenuation produced by EEDQ remained constant for at least 80 min. In conclusion, the effects of histamine and thioperamide at the H3 receptor are readily reversible, whereas EEDQ appears to be an irreversible antagonist; desensitization of the H3 receptor does not occur.