The influence of methysergide on 5-hydroxytryptamine-induced changes in regional distribution of blood flow

Forsyth, Ralph P.; Saxena, Pramod R.

doi:10.1111/j.2042-7158.1978.tb13303.x

Cited by 10 publications

(2 citation statements)

References 15 publications

(2 reference statements)

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“…9 Previous reports indicated beneficial effects of intra-venous administration of 5-HT in this syndrome, 10 and relates to its ability to decrease arteriovenous shunting. Proserotonin properties of the anti-migrainous drugs, methysergide 11 and ergotamine, 12 which constricted arteriovenous shunts of the head, 12 have been described. As the cerebral blood vessels are more sensitive to 5-HT 13 it seems reasonable to postulate that the arteriovenous shunts of the head are under tonic control of plasma-free 5-HT.…”

Section: Discussionmentioning

confidence: 99%

Serotonin: Change in Plasma‐free Level and Urinary Excretion after LM 5008 and Reserpine

Uzan¹,

Kabouche²,

Imbault³

et al. 1979

Headache

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SYNOPSISLM 5008, a potent 5-HT uptake inhibitor, induced an increase in plasma-free 5-HT level in a higher proportion than its metabolite 5-HIAA. In contrast, reserpine provoked a greater rise in 5-HIAA than in 5-HT, indicating stimulation of 5-HT turnover. LM 5008 potentiated the effects of reserpine on bound and free 5-HT and 5-HIAA levels but potentiated more the plasma-free 5-HT (4 times) than 5-HIAA (2.5 times), over reserpine-induced increases. Moreover, the rise in urinary excretion of 5-HT induced by reserpine was potentiated by LM 5008, whereas 5-HIAA was decreased. The differences between these two drugs implies that they do not act on the same platelet site. Since migraine has been proposed as a "low 5-HT syndrome," LM 5008 may be useful as an anti-migrainous agent.

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Section: Discussionmentioning

confidence: 99%

Serotonin: Change in Plasma‐free Level and Urinary Excretion after LM 5008 and Reserpine

Uzan¹,

Kabouche²,

Imbault³

et al. 1979

Headache

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“…The human studies focusing on the importance of 5‐HT inspired the development of the first triptan, sumatriptan, by P. Humphrey of Glaxo (29). In this work he was also inspired by the finding of Saxena of an ‘atypical’ receptor being responsible for the vasoconstrictor effects of methysergide in the carotid vascular bed studied with the arteriovenous shunt model (29–31).…”

Section: The Development Of Migraine Drugsmentioning

confidence: 99%

Finding New Drug Targets for the Treatment of Migraine Attacks

2009

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No new preventive drugs specific to migraine have appeared for the last 20 years and existing acute therapies need improvement. Unfortunately, no animal models can predict the efficacy of new therapies for migraine. Because migraine attacks are fully reversible and can be aborted by therapy, the headache- or migraine-provoking property of naturally occurring signalling molecules can be tested in a human model. This model has predicted efficacy of nitric oxide synthase inhibition and calcitonin gene-related peptide receptor blockade. The pharmaceutical industry should pay more attention to human models, although methods are different from normal target validation.

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Tissue blood flow and cephalic arteriovenous shunting in cats following administration of indalpine, a selective inhibitor of 5‐hydroxytryptamine uptake

Saxena

Tangri

1983

Drug Development Research

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Saxena, P.R., and K.K. Tangri: Tissue blood flow and cephalic arteriovenous shunting in cats following administration of indalpine, a selective inhibitor of 5-hydroxytryptamine uptake. Drug Dev. Res. 3:271-280, 1983. A number of observations indicate that a decrease in plasma 5-hydroxytryptamine (5-HT) level may lead to a diminished tissue perfusion and an opening of arteriovenous (AV) anastomoses in the head during migraine headaches. Indeed, some antimigraine drugs and the amine itself decrease the shunting of radioactive microspheres over the cephalic circulation in the experimental animals. Since indalpine selectively inhibits 5-HT uptake mechanisms and increases plasma 5-HT level, we have investigated the effects of the drug (1, 2, and 4 mg.kg-') on tissue blood flow and on AV shunting using the radioactive microsphere method in anesthetized cats. lndalpine caused minimal systemic hemodynamic effects; only a moderate (14%) hypotension resulted with the highest dose. Regionally, the drug increased blood flow to brain, intestines, mesentery + pancreas, and skeletal muscles. Both total peripheral AV-shunting (as indicated by the microsphere content of the lungs) and jugular venous AV-shunting (as measured by microspheres in the jugular venous blood) were decreased by the drug. These hemodynamic changes resemble those occurring during 5-HT infusions. It is suggested that indalpine may be of therapeutic value in migraine since it decreased AV-shunting across the cephalic circulation.

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The influence of methysergide on 5-hydroxytryptamine-induced changes in regional distribution of blood flow

Cited by 10 publications

References 15 publications

Serotonin: Change in Plasma‐free Level and Urinary Excretion after LM 5008 and Reserpine

Serotonin: Change in Plasma‐free Level and Urinary Excretion after LM 5008 and Reserpine

Finding New Drug Targets for the Treatment of Migraine Attacks

Tissue blood flow and cephalic arteriovenous shunting in cats following administration of indalpine, a selective inhibitor of 5‐hydroxytryptamine uptake

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