5-HT1C receptor activation: a key step in the initiation of migraine?

Fozard, John R.; Gray, John A.

doi:10.1016/0165-6147(89)90061-8

Cited by 68 publications

(47 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is conceivable that the therapeutic effects of the two ergots, presumably exerted through cerebral vascular constriction (Bowman & Rand, 1980), overshadow some possible 5-HT1c receptor stimulation. The present data therefore suggest a need to regard the hypothesis of Fozard & Gray (1989) with some caution though they are not sufficient to reject it. In addition, m-CPP also causes a considerable release of hypothalamic 5-HT (Pettibone & Williams, 1984) which could play an additional role in the production of headache.…”

Section: Resultsmentioning

confidence: 77%

“…Ergotamine has also been measured in human cerebrospinal fluid after oral administration of a therapeutic dose (Ala-Hurula et al, 1979) although some concern has been expressed about the specificity of the analytical method used in this study . These data suggest that some headache might be expected with ergots if the hypothesis of Fozard & Gray (1989) is correct for, given the high agonistic potency of the compounds, even a small amount of brain penetration should result in some activation of cerebral 5-HT1c receptors. It is conceivable that the therapeutic effects of the two ergots, presumably exerted through cerebral vascular constriction (Bowman & Rand, 1980), overshadow some possible 5-HT1c receptor stimulation.…”

Section: Resultsmentioning

confidence: 97%

“…The incidence of headache was significantly greater in subjects with a personal or family history of migraine. Fozard & Gray (1989) based their argument on the relative high affinity of m-CPP for 5-HT1c receptors (Hoyer, 1989), its relative high potency as an enhancer of inositol phosphate levels in pig choroid plexus (Schoeffter & Hoyer, 1989) and its selectivity for 5-HT1c receptors over other 5-HT1 receptor subtypes and 5-HT2 receptors (Hoyer, 1989).…”

Section: Introductionmentioning

confidence: 99%

“…

…”

mentioning

confidence: 99%

See 3 more Smart Citations

The antimigraine drugs ergotamine and dihydroergotamine are potent 5‐HT_1C receptor agonists in piglet choroid plexus

Brown

Patch

Kaumann

1991

British J Pharmacology

View full text Add to dashboard Cite

1 Fozard & Gray (1989) proposed that migraine is mediated by stimulation of 5-HT1c receptors. We have examined the interaction of two effective anti-migraine agents, ergotamine and dihydroergotamine (DHE), with these receptors. Binding (inhibition of labelling by [3H]-mesulergine) and agonist activity (phosphoinositide hydrolysis) were measured in piglet choroid plexus, a tissue rich in 5-HT1c receptors.2 The pKD for [3H]-mesulergine binding was 8.4. Ergotamine and DHE both inhibited [3H]-mesulergine binding with a pKD of 7.1. This was similar to the potency of m-chlorophenylpiperazine (m-CPP) (pKD 7.4) and rather less than that of 5-hydroxytryptamine (5-HT) (pKD 8.1).3 Both ergotamine and DHE were full agonists (pEC50s 7.5 and 7.6 respectively) with potencies similar to that of 5-HT (pEC50 7.7) and greater than that of m-CPP (pEC50 7.1). Mesulergine 1i-7M produced near-parallel rightward shifts of the concentration-response curves for all these agents of 1.8-2.2 log units, consistent with an action of the agonists at the same receptor. 4 There was no effect of prazosin, spiperone, mepyramine or atropine on the phosphoinositide hydrolysis induced by ergotamine, ruling out an action via ocl-adrenoceptors, 5-HT2, histamine H1, or muscarinic receptors.5 It is concluded that, together with 5-HT, ergotamine and DHE are the most potent 5-HT1c agonists reported so far. These findings do not support the theory that 5-HT1c receptor activation causes migraine.

show abstract

Section: Resultsmentioning

confidence: 77%

Section: Resultsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

“…

…”

mentioning

confidence: 99%

See 2 more Smart Citations

The antimigraine drugs ergotamine and dihydroergotamine are potent 5‐HT_1C receptor agonists in piglet choroid plexus

Brown

Patch

Kaumann

1991

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…This hypotheses stemmed principally from an observation by Brewerton et alJ' that m-chlorophenylpiperazine (mCPP) induced a high incidence of migraine-like headache following oral administration: of subjects with a personal or family history of migraine, 90% developed severe headache. mCPP has higher affinity for 5-HT l c receptors over other 5-HT 1 subtypes or 5-HT z receptors (see 76 for references). Further support for an involvement of 5-HT l c receptors in migraine came from the knowledge that pizotifen and cyproheptadine, used for the prophylactic treatment of migraine, are potent 5-HT l c receptor antagonists although both these agents have additional actions at other receptors.…”

Section: Comparison Of Safety Profile the Ergotsmentioning

confidence: 99%

Migraine, Serotonin and Sumatriptan

Connor¹,

Feniuk²,

Lloyd³

et al. 1992

Vascular Medicine Review

View full text Add to dashboard Cite

Distribution of the 5-hydroxytryptamine2C receptor protein in adult rat brain and spinal cord determined using a receptor-directed antibody: Effect of 5,7-dihydroxytryptamine

Sharma

Punhani

Fone

1997

Synapse

View full text Add to dashboard Cite

A synthetic peptide, corresponding to the N-terminal decapeptide (+Y11C12) of the rat 5-hydroxytryptamine2C (5-HT2C) receptor protein was used to produce a sheep polyclonal antiserum. Western blot analysis showed that the resultant antibody G241 recognised two membrane proteins, one (55 kDa) approximating the molecular mass of the 5-HT2C receptor (52 kDa) and a second (63 kDa), which may be a glycosylated form of the receptor protein. HEK 293 cells transfected with human 5-HT2C cDNA displayed intense cell surface immunoreactivity with the 5-HT2C antiserum, which was completely prevented by incubating the antibody with the synthetic 5-HT2C peptide (10 microM), whilst neither non-immune serum nor untransfected cells displayed any immunoreactivity. A radioimmunoassay was developed to quantify the regional distribution of 5-HT2C-like immunoreactivity (LI) in the adult rat brain. The choroid plexus contained five-fold higher levels of 5-HT2C-LI than any brain region but high levels were found in the frontal cortex, septum, hypothalamus, and striatum, intermediate levels in the thalamus and midbrain, and lower levels in brainstem, cerebellum, and spinal cord. In rat cortical membranes, the B(max) value from [3H]-mesulergine binding was ten-fold lower than 5-HT2C-LI levels determined by radioimmunoassay, which may reflect measurement of internalised receptor protein by radioimmunoassay which is not detected with conventional 5-HT2C ligands. Ten days after depletion of 5-HT with the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), there was a significant increase in 5-HT2C-LI in the choroid plexus and the ventral cervical spinal cord, suggesting that receptors therein are located post-synaptic to destroyed serotonergic nerve terminals. In contrast, the significant reduction in 5-HT2C-LI observed in the midbrain, brainstem, and dorsal thoracic spinal cord following 5,7-DHT implies that 5-HT2C receptors may be located on 5-HT nerve terminals in these regions.

show abstract

5-HT1C receptor activation: a key step in the initiation of migraine?

Cited by 68 publications

References 17 publications

The antimigraine drugs ergotamine and dihydroergotamine are potent 5‐HT_1C receptor agonists in piglet choroid plexus

The antimigraine drugs ergotamine and dihydroergotamine are potent 5‐HT_1C receptor agonists in piglet choroid plexus

Migraine, Serotonin and Sumatriptan

Distribution of the 5-hydroxytryptamine2C receptor protein in adult rat brain and spinal cord determined using a receptor-directed antibody: Effect of 5,7-dihydroxytryptamine

Contact Info

Product

Resources

About

5-HT1C receptor activation: a key step in the initiation of migraine?

Cited by 68 publications

References 17 publications

The antimigraine drugs ergotamine and dihydroergotamine are potent 5‐HT1C receptor agonists in piglet choroid plexus

The antimigraine drugs ergotamine and dihydroergotamine are potent 5‐HT1C receptor agonists in piglet choroid plexus

Migraine, Serotonin and Sumatriptan

Distribution of the 5-hydroxytryptamine2C receptor protein in adult rat brain and spinal cord determined using a receptor-directed antibody: Effect of 5,7-dihydroxytryptamine

Contact Info

Product

Resources

About

The antimigraine drugs ergotamine and dihydroergotamine are potent 5‐HT_1C receptor agonists in piglet choroid plexus

The antimigraine drugs ergotamine and dihydroergotamine are potent 5‐HT_1C receptor agonists in piglet choroid plexus