Disease relevance of CP 122288

• No acute antimigraine efficacy of CP-122,288, a highly potent inhibitor of neurogenic inflammation: results of two randomized, double-blind, placebo-controlled clinical trials [1].
• Potentially, CP-122,288 may be of use for the acute treatment of migraine, without the risk of cardiovascular side-effects [2].

High impact information on CP 122288

• 5-Carboxamido-tryptamine, CP-122,288 and dihydroergotamine but not sumatriptan, CP-93,129, and serotonin-5-O-carboxymethyl-glycyl -tyrosinamide block dural plasma protein extravasation in knockout mice that lack 5-hydroxytryptamine1B receptors [3].
• CP-122,288 (1 nmol kg), 5-CT (1 nmol/kg), and dihydroergotamine (72 nmol/kg) inhibited plasma protein extravasation within dura mater after electrical trigeminal ganglion stimulation in both wild-type and knockout mice, which suggests that these agonists act predominantly via receptors other than 5-HT1B [3].
• The aim of this study was to examine whether GR-127,935, a 5-HT1B/1D receptor antagonist, blocks the inhibitory effects of sumatriptan, CP-122,288 and 5-carboxamidotryptamine (5-CT) on plasma protein extravasation, within guinea pig and rat dura matter, following electric stimulation of the trigeminal ganglion [4].
• Interestingly, doses of CP-122,288 that inhibit neurogenic inflammation in rat dura mater (0.3-300 ng kg-1) were demonstrated to be devoid of vasoconstrictor activity in either the carotid or coronary vascular beds of dog [2].
• CP-122,288 (30 and 300 ng kg-1, i.v., P < 0.01 and P < 0.05, respectively) produced a complete inhibition of plasma protein leakage which was consistent with its effects when administered prior to trigeminal ganglion stimulation [2].

Chemical compound and disease context of CP 122288

• Conformationally restricted sumatriptan analogues, CP-122,288 and CP-122,638 exhibit enhanced potency against neurogenic inflammation in dura mater [5].

Biological context of CP 122288

• 4. In a separate series of studies in the anaesthetized rat, CP-122,288 (0.003-3 micrograms kg-1 i.v.) produced no change in either heart rate or mean arterial blood pressure, thus demonstrating that doses of CP-122,288 which inhibit plasma protein leakage in rat dura, are devoid of hemodynamic effects [2].

Anatomical context of CP 122288

• 3. At all doses tested, CP-122,288 did not inhibit plasma protein extravasation measured in extracranial tissues such as the lower lip, eyelid, and conjunctiva [2].
• Suppression by the sumatriptan analogue, CP-122,288 of c-fos immunoreactivity in trigeminal nucleus caudalis induced by intracisternal capsaicin [6].
• However, CP-122,288 was only approximately 2-fold more potent than sumatriptan at inhibiting neurogenically mediated contractions of the dog saphenous vein [7].
• It is concluded that CP-122,288 exhibits a prejunctional selectivity in the meninges to inhibit dural plasma protein extravasation independent of 5-HT1D alpha and 5-HT1D beta receptor activation [7].
• [3H]5-CT appeared to label 5-HT1B/5-HT1D sites in the substantia nigra, globus pallidus and caudate/putamen, as the binding in these regions was displaced by the 5-HT1B/1D receptor selective agents sumatriptan, CP-122,288 and GR-127,935 [8].

Associations of CP 122288 with other chemical compounds

• The failing soldiers have included the NK-1 antagonists, some second-generation 5-HT(1B/1D) agonists, CP-122,288, 4991W93, the neurosteroid ganaxolone, selective 5-HT(1F) (LY334370) and 5-HT(1D) agonists (PNU-142,633), and the endothelin-1 antagonist bosentan [9].

Analytical, diagnostic and therapeutic context of CP 122288

• We evaluated the acute antimigraine efficacy of intravenous and oral CP-122,288 in two double-blind studies [1].
• In a crossover design, patients randomly received 31.25 microg of CP-122,288 intravenously, placebo, or both [1].
• By administration of the compound 5 min after completing the phase of electrical stimulation, this protocol permitted the evaluation of the activity of CP-122,288 on an ongoing and established inflammatory event [2].

References