Posted by Steve H. in Germany on June 07, 1999 at 15:28:50:
In Reply to: Re: OK...if they are shadows... posted by Steve W on June 07, 1999 at 11:37:57:
Steve,
Dihydroergotamine. Brand name: Migranal.
See my post: About medications - may help the uninitiated. Below is an excerpt from Clinical Pharmacology Online.
Hope this helps!
Steve sends...
Description: Dihydroergotamine (DHE) is a semisynthetic ergot alkaloid administered parenterally or intranasally to treat migraine. Although DHE injection has been used for many years in the treatment of migraine, it is now considered more appropriate for treating severe cases since less toxic agents, such as naproxen, are more efficacious for moderate cases.[102] Intranasal dihydroergotamine was successful in 47—70% of patients with migraine headache pain (assessed four hours after treatment) compared with placebo response rates of 22—35%.[1050] [1471] Dihydroergotamine was approved by the FDA in 1946. The nasal spray dosage form (e.g., Migranal® by Novartis) was approved for acute treatment of migraine with or without aura on 12/10/97.
Mechanism of Action: The pharmacologic actions of ergot alkaloids are complex. Dihydroergotamine (DHE) binds with high affinity to all known 5-HT1 receptors as well as a number of other biogenic amine receptors, such as 5-HT2 (subtypes A and C), alpha1 and alpha2-adrenergic receptors, and DA2 dopaminergic receptors. The therapeutic effect of DHE in the treatment of migraine is thought to be due primarily to agonist activity at 5-HT1 subtype D receptors. The efficacy of sumatriptan, a selective serotonin agonist, in the treatment of migraine is attributed to agonist activity at 5-HT1 receptor subtypes B and D. It is hypothesized that activation of 5-HT1 receptors (subtypes B and D) located on intracranial blood vessels may cause vasoconstriction of large intracranial conductance arteries and closure of arterio-venous anastomoses which correlates with the relief of migraine headache. Another hypothesis is that activation of 5-HT1 receptors on sensory nerve endings of the trigeminal system may inhibit the release of pro-inflammatory neuropeptides (e.g., substance P and calcitonin gene-related peptide (CGRP) from the trigeminal nerve). Substance P and CGRP may be involved in the generation of pain during a migraine episode.
In the periphery, DHE causes vasoconstriction by stimulating alpha-adrenergic receptors. Although it is also a competitive alpha-adrenergic blocker at higher doses, this effect is somewhat masked by the drug's alpha-adrenergic agonist activity. With therapeutic doses, DHE also inhibits reuptake of norepinephrine, thereby increasing vasoconstriction. Effects of DHE on blood pressure are unpredictable, but the drug vasoconstricts capacitance vessels more than resistance vessels. Therefore, it increases venous return and decreases venous stasis and pooling. Dihydroergotamine has less vasoconstrictor activity than ergotamine. Although DHE possesses oxytocic properties; its oxytocic activity is less than that of ergotamine and much less than that of ergonovine or methylergonovine.
Pharmacokinetics: Dihydroergotamine (DHE) is incompletely and irregularly absorbed from the GI tract and thus is administered parenterally or intranasally. Following intranasal administration, the bioavailability of DHE is roughly 32% relative to injectable administration. Absorption after intranasal administration is variable, probably reflecting intersubject differences in absorption and the technique used for self-administration. The intranasal dosage form exhibits linear pharmacokinetics between doses of 1—4 mg. Peak plasma concentrations after intranasal or subcutaneous administration occur about 45 minutes after the dose (range 30—60 minutes). Onset of relief from a migraine headache depends on route of administration and how soon the drug is given after the onset of symptoms. Onset of migraine pain relief after intranasal administration usually begins within 30 minutes. After IM administration, onset of action is usually 15—30 minutes, and the duration is 3—4 hours. Pain relief is usually observed within 5 minutes after intravenous administration. The drug is 90—93% bound to plasma proteins.
Extensive metabolism of DHE occurs in the liver. Three active metabolites and two inactive metabolites have been identified. The metabolites include 8'-beta-hydroxydihydroergotamine and dihydrolysergic acid amide, which are further oxidized to the carboxylic acid derivative and to dihydrolysergic acid, respectively. Only 10% of a dose is excreted renally, and the rest is excreted through the biliary-fecal route. Following intranasal administration, urinary recovery of the parent compound is roughly 2% of the dose.
[Revised 12/07/1998]