Effect of the CGRP receptor antagonist BIBN4096BS in human cerebral, coronary and omental arteries and in SK-N-MC cells

Edvinsson, Lars; Alm, Rikard; Shaw, Duncan; Rutledge, Ruth Z.; Koblan, Kenneth S.; Longmore, J.; Kane, Stefanie A.

doi:10.1016/s0014-2999(01)01532-1

Cited by 106 publications

(87 citation statements)

References 18 publications

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“…The authors explained it by insufficient dissociation of BIBN4096BS from the receptors. Similar observations have been made in our previous study on human coronary arteries when relatively higher concentrations of BIBN4096BS (3 and 10 nM) were used (Edvinsson et al, 2002). Furthermore, recent studies carried out by Gupta et al (2004) showed similar results in both proximal and distal regions of the human coronary vascular bed.…”

Section: Sheykhzade Et Alsupporting

confidence: 90%

“…In addition, we have recently shown that BIBN4096BS competitively antagonized the CGRP-induced relaxations in isolated human cerebral arteries (pA 2 value of 10.1) (Edvinsson et al, 2002). In human coronary arteries the situation is somewhat different; we observed that the vessels were less responsive to CGRP but equally sensitive to BIBN4096BS (pA 2 value of 10.4) Edvinsson et al, 2002). These findings are in accord with the data recently presented by Gupta et al (2004).…”

Section: Introductionsupporting

confidence: 92%

“…After the first CGRP control curve, the arteries were stimulated twice with KPSS and incubated with BIBN4096BS for 30 min before the second CGRP CRC was performed. This preincubation time (30 min) is the same that was used in our previous study on human cerebral arteries, where BIBN4096BS concentrationdependently induced a significant parallel-rightward shift in the log CGRP concentration-relaxation curve (Edvinsson et al, 2002). Time control studies showed no sign of tachyphylaxis to CGRP in these vessels as the first and the second CGRP curves were completely overlapping (data not shown).…”

Section: Concentration-response Curves (Crcs)mentioning

confidence: 74%

“…In a previous study carried out by Verheggen et al (2002) on isolated human temporal arteries, an incubation time of 2 h with BIBN4096BS was used versus 30 min of incubation in the present study and also in the previous studies carried out by Edvinsson et al (2002) on isolated human coronary and cerebral arteries. Furthermore, Verheggen et al (2002) showed that BIBN4096BS at the concentration of 1 mM caused additional blockage, which was insurmountable.…”

Section: Sheykhzade Et Almentioning

confidence: 94%

“…Both studies showed reduction in maximum relaxation to CGRP as the concentration of BIBN4096BS was increased. In addition, omental arteries of man (intestinal arteries) did not respond to CGRP (Edvinsson et al, 2002). Most strikingly, BIBN4096BS demonstrates species specificity with 100-fold lower affinity for the rat versus human CGRP 1 receptor.…”

Section: Introductionmentioning

confidence: 95%

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Noncompetitive antagonism of BIBN4096BS on CGRP‐induced responses in human subcutaneous arteries

Sheykhzade

Lind

Edvinsson

2004

British J Pharmacology

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1 We investigated the antagonistic effect of 1-piperidinecarboxamide, N-[2-[[5amino-l-[[4-(4-pyridinyl)-l-piperazinyl]carbonyl]pentyl]amino]-1- [(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl) (BIBN4096BS) on the calcitonin gene-related peptide (CGRP)-induced responses by using isometric myograph and FURA-2 technique in human subcutaneous arteries removed in association with abdominal surgery. 2 BIBN4096BS, at the concentration of 1 pM, had no significant effect on the CGRP-induced relaxation in these vessels. 3 At the concentration of 10 pM, BIBN4096BS had a competitive antagonistic-like behaviour characterized by parallel rightward shift in the log CGRP concentration-tension curve with no depression of the E max . 4 At the higher concentrations (0.1 and 1 nM), BIBN4096BS had a concentration-dependent noncompetitive antagonistic effect on the CGRP-induced responses. 5 The efficacy and potency of CGRP was significantly greater in the smaller (lumen diameter B200 mm) human subcutaneous arteries compared to the larger ones. 6 The apparent agonist equilibrium dissociation constant, K A , for CGRP 1 receptors in the human subcutaneous arteries was approximately 1 nM. Analysis of the relationship between receptor occupancy and response to CGRP indicates that the receptor reserve is relatively small. 7 Using reverse transcriptase-polymerase chain reaction (RT-PCR), the presence of mRNA sequences encoding the calcitonin receptor-like receptor, receptor activity modifying protein (RAMP1, RAMP2, RAMP3) and receptor component protein were demonstrated in human subcutaneous arteries, indicating the presence of CGRP 1 -like receptor and the necessary component for the receptor activation. 8 In conclusion, the inhibitory action of BIBN4096BS at the low concentration (10 pM) on the CGRP-tension curve (but not intracellular calcium concentration ([Ca 2 þ ] i ) resembles what is seen with a reversible competitive antagonist. However, at the higher concentrations (0.1 and 1 nM), BIBN4096BS acts as a selective noncompetitive inhibitor at CGRP 1 receptors in human subcutaneous arteries.

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Section: Sheykhzade Et Alsupporting

confidence: 90%

Section: Introductionsupporting

confidence: 92%

Section: Concentration-response Curves (Crcs)mentioning

confidence: 74%

Section: Sheykhzade Et Almentioning

confidence: 94%

Section: Introductionmentioning

confidence: 95%

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Noncompetitive antagonism of BIBN4096BS on CGRP‐induced responses in human subcutaneous arteries

Sheykhzade

Lind

Edvinsson

2004

British J Pharmacology

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Advent of a New Generation of Antimigraine Medications

Recober

Russo

2007

Handbook of Contemporary Neuropharmacology

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This chapter will address recent developments in the treatment of migraine. The recent promising clinical trials using a new antimigraine medication, BIBN4096BS, heralds the advent of a new generation of therapeutics. BIBN4096BS targets the receptor for the neuropeptide calcitonin gene–related peptide (CGRP), which appears to play a causal role in migraine pain. We will discuss the rationale and therapeutic implications of modulating CGRP, including its potential for acting at multiple sites in the trigeminovasculature. We will then discuss the currently used acute and preventative pharmacological treatments. Of particular interest is the increasing evidence that antiepileptic drugs may be an effective prophylactic treatment for migraine. Future strategies to selectively downregulate CGRP synthesis and the potential use of migraine drugs for other forms of trigeminal‐mediated pain, such as temporomandibular disorder and trigeminal neuralgia, will be explored.

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Calcitonin receptor‐like receptor (CLR), receptor activity‐modifying protein 1 (RAMP1), and calcitonin gene‐related peptide (CGRP) immunoreactivity in the rat trigeminovascular system: Differences between peripheral and central CGRP receptor distribution

Lennerz

Rühle

Ceppa

et al. 2008

J of Comparative Neurology

292

221

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Calcitonin gene-related peptide (CGRP) is a key mediator in primary headaches including migraine. Animal models of meningeal nociception demonstrate both peripheral and central CGRP effects; however, the target structures remain unclear. To study the distribution of CGRP receptors in the rat trigeminovascular system we used antibodies recognizing two components of the CGRP receptor, the calcitonin receptor-like receptor (CLR) and the receptor activity-modifying protein 1 (RAMP1). In the cranial dura mater, CLR and RAMP1 immunoreactivity (-ir) was found within arterial blood vessels, mononuclear cells, and Schwann cells, but not sensory axons. In the trigeminal ganglion, besides Schwann and satellite cells, CLR- and RAMP1-ir was found in subpopulations of CGRP-ir neurons where colocalization of CGRP- and RAMP1-ir was very rare ( approximately 0.6%). CLR- and RAMP1-ir was present on central, but not peripheral, axons. In the spinal trigeminal nucleus, CLR- and RAMP1-ir was localized to "glomerular structures," partly colocalized with CGRP-ir. However, CLR- and RAMP1-ir was lacking in central glia and neuronal cell bodies. We conclude that CGRP receptors are associated with structural targets of known CGRP effects (vasodilation, mast cell degranulation) and targets of unknown function (Schwann cells). In the spinal trigeminal nucleus, CGRP receptors are probably located on neuronal processes, including primary afferent endings, suggesting involvement in presynaptic regulation of nociceptive transmission. Thus, in the trigeminovascular system CGRP receptor localization suggests multiple targets for CGRP in the pathogenesis of primary headaches.

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Effect of the CGRP receptor antagonist BIBN4096BS in human cerebral, coronary and omental arteries and in SK-N-MC cells

Cited by 106 publications

References 18 publications

Noncompetitive antagonism of BIBN4096BS on CGRP‐induced responses in human subcutaneous arteries

Noncompetitive antagonism of BIBN4096BS on CGRP‐induced responses in human subcutaneous arteries

Advent of a New Generation of Antimigraine Medications

Calcitonin receptor‐like receptor (CLR), receptor activity‐modifying protein 1 (RAMP1), and calcitonin gene‐related peptide (CGRP) immunoreactivity in the rat trigeminovascular system: Differences between peripheral and central CGRP receptor distribution

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