Disease relevance of Immepip

• Immepip (30nM) induced a modest, but significant increase (113+/-2% of basal) in [(35)S]-GTPgammaS binding to synaptosomal membranes, an effect prevented by clobenpropit (1muM) and by pre-treatment with pertussis toxin [1].
• Coadministration of immepip (1 mg/kg) with L-dopa (15 mg/kg) was associated with significantly less total dyskinesia than L-dopa alone [2].
• Thus, we tested whether the histamine H3 receptor agonists immepip and imetit can alleviate LID in the MPTP-lesioned marmoset model of Parkinson's disease [2].
• When dyskinesia was separately rated as chorea and dystonia, coadministration of L-dopa with either immepip or imetit (both 10 mg/kg) significantly reduced chorea but had no effect on dystonia [2].

Psychiatry related information on Immepip

• 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 [3].

High impact information on Immepip

• A new potent and selective histamine H3 receptor agonist, 4-(1H-imidazol-4-ylmethyl)piperidine [4].
• Zebrafish larvae were exposed to 1, 10 or 100muM of the H(1) ligand pyrilamine, the H(2) ligand cimetidine and the H(3) ligands thioperamide and immepip for 5 days [5].
• In thalamus synaptosomes depolarisation-induced, Ca(2+)-dependent glutamate release was inhibited by histamine (1muM, 25+/-4% inhibition) and immepip (30nM, 38+/-5% reduction) [1].
• Immepip (1 microM) also inhibited the depolarization-induced release of [3H]dopamine from substantia nigra pars reticulata slices, by 38 +/- 3% [6].
• In striatal membranes bearing significant levels of histamine H3 receptors (72 +/- 14 fmol/mg protein), the H3 agonist immepip (1 microM) increased [35S]GTPgammaS binding to 119 +/- 2% of basal, an effect prevented by the H3 antagonist clobenpropit and by pre-treatment with pertussis toxin [7].

Biological context of Immepip

• The accumulation of [3H]cAMP induced by 1 microM SKF-81297 was inhibited in a concentration-dependent manner by the selective H3 receptor agonist immepip (maximal inhibition 60+/-5%, IC50 13 +/- 5 nM) [7].
• Neither the density of [3H]SCH-23390 binding sites (D1 receptors) nor the inhibition by SKF-81297 were affected by 1 microM immepip, ruling out a direct interaction between D1 and H3 receptors [7].

Anatomical context of Immepip

• The potencies (pA(2) values) observed at the guinea pig jejunum were 8.4 and 6.2 for the immepip homologues VUF 4929 and VUF 4735, respectively, whereas on the electrically evoked release of [(3)H]-noradrenaline from cortical slices the pA(2) values were 7.1 and 5.5 for VUF 4929 and VUF 4735, respectively [8].
• When administered directly into the spinal subarachnoid space, immepip (15-50 microg, i.t.) and R-alpha-methylhistamine (50 microg, i.t.) had no effect in rats on the tail flick and hot plate tests, but produced a dose- and time-dependent inhibition (90-100%) of nociceptive responses on the tail pinch test [9].
• Moreover, immepip, but not the (R)-alpha-methylhistamine, showed almost a tenfold higher agonistic potency in the rat cerebral cortex than in the guinea pig jejunum [8].
• The decreased histamine release after peripheral injection of immepip indicates that this novel agonist readily crosses the blood-brain barrier, making it a potential candidate for in vivo histamine H3 receptor studies [10].
• We investigated the effect of the new potent and selective histamine H3 receptor agonist, immepip, and the histamine H3 receptor antagonist, clobenpropit, on in vivo neuronal histamine release from the anterior hypothalamic area of urethane-anesthetized rats, using microdialysis [10].

Associations of Immepip with other chemical compounds

• In perfused ileal segments, specific agonists acting at histamine H3 receptors, ((R)-alpha-methylhistamine and immepip, 1 nmol-10 micromol/l), did not cause any change in the threshold pressure for triggering the peristaltic wave, or in the rise of the perfusion pressure during the emptying phase [11].
• Hydroxyzine prevents isolation-induced vocalization in guinea pig pups: comparison with chlorpheniramine and immepip [12].

Analytical, diagnostic and therapeutic context of Immepip

• Using the microdialysis technique in freely moving rats, we found that the histaminergic H3 agonists R-alpha-methylhistamine (RAMH) and immepip, directly administered into the BLA, augmented spontaneous release of ACh in a similar manner [13].
• 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 [3].

References