Olcegepant

Research use only, not for human use.

The first small molecule selective CGRP antagonist with Ki of 14.4 nM for hCGRP.

The first small molecule selective CGRP antagonist with Ki of 14.4 nM for hCGRP; inhibits the effects of CGRP, released by stimulation of the trigeminal ganglion, on facial blood flow in marmoset monkeys (1-30mg/kg, i.v.).

Olcegepant possesses higher affinity for the human CGRP receptor than the endogenous ligand CGRP and 150-fold higher affinity compared to the peptidic antagonist CGRP8-37. Olcegepant reverses CGRP-mediated vasodilation in human cerebral vessels and inhibits neurogenic vasodilation in a surrogate animal model of migraine pathophysiology. Olcegepant (BIBN4096BS) is extremely potent at primate CGRP receptors exhibiting an affinity (Ki) for human CGRP receptors of 14.4±6.3 (n=4) pM. Several lines of evidence suggest that a calcitonin-gene related peptide (CGRP) receptor antagonist may serve as a novel abortive migraine treatment. Olcegepant (BIBN4096BS) exhibits competitive antagonism at the CGRP receptor present in SK-N-MC cells. Isolated human cerebral, coronary, and omental arteries are studied with a sensitive myograph technique. CGRP induces a concentration-dependent relaxation that is antagonized by Olcegepant in a competitive manner.

Olcegepant (BIBN4096BS) in doses between 1 and 30 μg/kg (i.v.) inhibits the effects of CGRP, released by stimulation of the trigeminal ganglion, on facial blood flow in marmoset monkeys. Pre-treatment with Olcegepant (900 μg/kg) inhibits the capsaicin-induced expression of Fos throughout the spinal trigeminal nucleus by 57%. In contrast, the expression of phosphorylated extracellular signal-regulated kinase in the trigeminal ganglion is not changed by Olcegepant pre-treatment. Olcegepant (0.3 to 0.9 mg/kg, i.v.) markedly reduces mechanical allodynia in CCI-ION rats. Olcegepant (0.6 mg/kg, i.v.) significantly reduces the number of c-Fos immunolabeled cells in spinal nucleus of the trigeminal nerve and upregulation of ATF3 transcript (a marker of neuron injury) but not that of interleukin-6 in trigeminal ganglion of CCI-ION rats.

BIBN-4096 | BIBN-4096BS | BIBN4096BS

GPCR/G Protein

CGRP Receptor

CGRP Receptor

Neurological Disease

——

204697-65-4

869.6451

C38H47Br2N9O5

>98% (HPLC)

DMSO: ≥ 50 mg/mL

O=C(N1CCC(N2C(NC3=C(C=CC=C3)C2)=O)CC1)N[C@H](CC4=CC(Br)=C(O)C(Br)=C4)C(N[C@H](C(N5CCN(C6=CC=NC=C6)CC5)=O)CCCCN)=O

Piperazine, 1-[3,5-dibromo-N-[[4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)-1-piperidinyl]carbonyl]-D-tyrosyl-L-lysyl]-4-(4-pyridinyl)-

(-20℃)

With Ice Pack

≥ 2 years