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H3 agonist immepip markedly reduces cortical histamine release, but only weakly promotes sleep in the rat

Pharmacological Research
Elsevier BV
Publication Date
DOI: 10.1016/s1043-6618(03)00094-x
  • Brain Histamine
  • H3 Receptor
  • Immepip
  • Brain Microdialysis
  • Sleep/Wake Cycle
  • Biology
  • Pharmacology


Abstract Presynaptic H3 receptors exert negative control on brain histamine synthesis and release and may thereby play a key role in the control of the sleep/wake cycle. This suggests that pharmacological stimulation by H3 receptor agonists may potentially decrease wakefulness and induce sleep. This study reports the effect of a potent and selective H3 agonist, immepip, on EEG assessed sleep/wake phases in Sprague–Dawley rats at doses that significantly modulate brain histamine release. Immepip injected intraperitoneally (i.p.) at 5 or 10 mg kg −1 induced a sustained decrease in cortical histamine efflux as measured by in vivo microdialysis. In a separate experiment, rats were prepared for EEG/EMG recording and evaluated during the dark phase of their light/dark cycle. The results showed that the same i.p. doses of 5 and 10 mg kg −1 of immepip was devoid of any significant impact on the sleep/wake phases (active awake, drowsiness and slow wave sleep), except for a slight, albeit significant, decrease in sleep onset latency. These results reveal that a marked H3 receptor agonist-mediated reduction in cortical histamine release is not corroborated by a significant sleep promoting effect and therefore question the hypnotic potential of H3 agonists.

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