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We are reporting an interesting case of pituitary macroadenoma. The patient presented with sudden, bifrontal, pulsating headache; photophobia; and an abducens nerve palsy, due to extension of the tumor into the cavernous sinus region. The headache resolved completely after a subcutaneous injection of sumatriptan.
Rabbit iliac arteries (IA) were almost unresponsive to the serotonin (5-HT1-like) receptor agonist sumatriptan under control conditions, whereas this agent elicited concentration-dependent contractions in IA rings given a moderate tone by threshold concentrations (EC10-EC20) of prostaglandin F2 alpha (PGF2 alpha), angiotensin II (AII), histamine, norepinephrine (NE), phenylephrine (PE), or potassium chloride. These results suggest that 5-HT1-like receptors are uncovered not only by histamine or thromboxane/prostaglandin receptor agonists, as shown in rabbit renal and femoral arteries, but also by various agonists in rabbit IA as shown in this study.
Systemic administration of nitroglycerin (NTG), a nitric oxide (NO) donor, in migraineurs triggers after several hours an attack of which the precise mechanisms are unknown. We found previously in rats that nitroglycerin (10 mg/kg s.c.) is able to increase significantly after 4 h the number of neuronal nitric oxide synthase (nNOS)-immunoreactive neurones in the cervical part of trigeminal nucleus caudalis. In the present experiments, we demonstrate that the 5-HT1B/D agonist sumatriptan (0.6 mg/kg s.c.) does not alter this phenomenon when given before NTG. By contrast, pretreatment with lysine acetylsalicylate (50 mg/kg i.m.) attenuates the NTG-induced nNOS expression in the superficial laminae of trigeminal nucleus caudalis. These findings suggest that effect of NTG on nNOS at a high dosage may involve the cycloxygenase pathway and that activation of the peripheral 5-HT1B/D receptors is not able to modify this effect. These data could help to better understand the role of NO in the pathogenesis of headaches and the action of antimigraine drugs.
The potency of dihydroergotamine (DHE) was determined at 13 neurotransmitter receptors using radioligand binding techniques. DHE is a potent agent (i.e. affinity value less than 100 nM) at 5-hydroxytryptamine1A (5-HT1A), 5-HT1C, 5-HT1D, 5-HT2, dopamine2, alpha1- and alpha2-adrenergic binding sites. DHE displays moderate affinity (i.e. affinity values = 100 - 1000 nM) for beta-adrenergic and dopamine1 sites and is completely inactive at 5-HT3, muscarinic and benzodiazepine receptors. These results were then compared to similar data on sumatriptan (formerly called GR 43175), a novel acute anti-migraine agent. The only pharmacological property shared by both agents is high affinity for 5-HT1D and 5-HT1A receptors. Therefore, these data suggest that 5-HT1D and/or 5-HT1A receptors may play an important role in the pathophysiology of migraine.
A female patient is described who had a four year long period of unilateral chronic paroxysmal hemicrania (CPH) which then became bilateral. For some years before the CPH started she suffered from periods of about one month with chronic hemicrania without nerve involvement. She also suffered from chronic fatigue, back pain, arthralgia, vertigo, chronic constipation and spontaneous ecchymoses. Blood tests showed chronic leukocytosis, low serum iron, and signs of inflammation in serum electrophoresis during the five years she was studied. CPH attacks could be provoked by breathing 6% carbon dioxide in air. Lumbar cerebrospinal fluid pressure was pathologically increased (30 cm water). The attacks decreased during indomethacin treatment but 275 mg was needed for satisfactory control of the attacks, i.e., more than the 150 mg which, according to the criteria for CPH, should be absolutely effective. Sumatriptan was found to suppress the CPH attacks as well as indomethacin. Due to these findings CPH is considered to be another manifestation of venous vasculitis. The beneficiary mechanism of indomethacin in CPH is considered to be due partly to its anti-inflammatory effects and partly to its reduction of the intracranial blood flow.
Very little has been written about headaches following electroconvulsive therapy (ECT) but the incidence has been estimated at 26%. Patients with a history of migraine occasionally have similar headaches precipitated by ECT. In addition, some patients may have headaches that persist for months after a series of ECT treatments, while some patients who have a preexisting headache problem report improvement with ECT. Serotonergic mechanisms have been proposed both for the efficacy of ECT and its tendency to produce headaches in susceptible patients. There have been no studies on the prophylaxis or treatment of post-ECT headache. While various strategies have been suggested for these headaches, even case reports documenting the efficacy of these strategies are lacking. We, therefore, report a case of severe, refractory, post-ECT headaches which responded to prophylactic treatment with sumatriptan.
OBJECTIVES: To document the relationship between the use of subcutaneous (SQ) sumatriptan (sum) and a change in frequency pattern of cluster headache (CH) in six patients. To discuss the clinical and pathophysiological implications of this observation in the context of available literature. BACKGROUND: Treatment with SQ sum may cause an increase in attack frequency of CH but data from literature are scant and controversial. METHODS: Six CH sum-naïve patients (three episodic and three chronic according to the International Headache Society (IHS) criteria) are described. RESULTS: All six patients had very fast relief from pain and accompanying symptoms from the drug but they developed an increase in attack frequency soon after using SQ sum. In all patients, the CH returned to its usual frequency within a few days after SQ sum was withdrawn or replaced with other drugs. Five patients were not taking any prophylactic treatment and SQ sum was the only drug prescribed to treat their headache. CONCLUSIONS: Physicians should recognize the possibility that treatment of CH with SQ sum may be associated with an increased frequency of headache attacks.
A patient was seen with secondary cluster headache whose acute pain responded promptly to sumatriptan. The headaches started after injury to the vertebral artery. This finding provides clinical affirmation of the existence of the trigeminal/cervical nuclear overlap that is central to this condition.
Measures of serotonin (5-HT) turnover in A. carolinensis forebrain increase acutely when males exhibit dominant social/territorial display routines, but decrease during submissive displays [Baxter et al., 2001a, b]. The present investigation sought to determine whether a difference in presynaptic regulatory receptors - one that might affect 5-HT flux - distinguish dominant vs. submissive anoles. Both 5-HT(1B) and 5-HT(1D) receptors are presynaptic regulators of output; this role is prominent at 5-HT terminals, where stimulation inhibits 5-HT release. Here, 3H-sumatriptan binding at sites similar to mammalian 5-HT(1B/D) receptors was significantly higher in forebrain regions of submissive anoles than in dominant cagemates; this receptor site seemed pharmacologically more like a 5-HT(1B) than a 5-HT(1D) receptor. Higher densities of presynaptic 5-HT(1B) receptors in subordinates than in dominants might account for differences in 5-HT flux (lower in subordinates than in dominants) observed in displaying anoles of different status. Knockout mice missing the 5-HT(1B) receptor show heightened male territorial aggressiveness, thus similar 5-HT regulatory mechanisms might influence the likelihood of dominance in both mammals and reptiles.
The purpose of this work was to study 'in vivo' the vascular responses of retinal vessels of New Zealand white rabbits to substance P (SP), neurokinin A (NKA), neurokinin B (NKB), senktide, capsaicin (CAPS), and calcitonin gene related peptide (CGRP) before and after selective antagonist administration. We examined the effects of these neuropeptides on the normal circulation in the optic nerve head of the rabbit. Drugs were injected via pars plana through a micropipette system. Ten minutes before perivascular injection of 10 nmol/l sumatriptan (to contract the vessel), a selective antagonist or its solvent was administered. Then, cumulative injection of the agonist was performed. The other eye was used as control. Direct measurement of retinal arteriole diameters was performed using digital angiography. The quantification of the relaxing effect is expressed as percentage related to the precontracted vascular diameter. Microinjection of SP (NK1 receptor agonist) up to 10 nmol/l induced a dose-dependent arteriolar dilating effect [E(max) (mean +/- SEM) 21.3 +/- 2.3%]. After the perivascular preinjection of 1 nmol/l L-668,169 or 1 nmol/l L-733,060 (NK1 receptor antagonists), the SP dose-response curve was shifted to the right. The same results were obtained with NKA (NK2 receptor agonist) which induced the most potent effect of all neuropeptides (E(max) 53.3+/-2.5%). The NK2 receptor antagonists L-659,877 and GR 159897 (1 nmol/l) strongly inhibited this arteriolar vasodilation. As for CGRP, doses up to 10 nmol/l induced a marked vasodilation (E(max) 41.1+/-0.4%) which decreased after microinjection of the selective antagonist CGRP8-37. The NK3 receptor agonists (senktide and NKB) showed a minor vasodilating effect (E(max) 5.1+/-1.2 and 8.0+/-0.9%, respectively). On the contrary, CAPS showed a marked dose-dependent vasodilating effect (E(max) 43.2+/-2.9%), antagonized by the tachykinin receptor antagonists and CGRP8-37. These results suggest, for the first time, the presence of NK1, NK2, and CGRP receptors on the retinal arteriolar wall of the rabbit.
The efficacy, safety, and tolerability of subcutaneous sumatriptan in the acute treatment of cluster headache were investigated in a multicenter study over a period of up to 1 year. A total of 2,031 attacks were evaluated in 52 patients. Therapy was successful in 88% of all attacks. Freedom from pain within 15 minutes in more than 90% of all attacks treated was reported by 42% of the patients, and no decline in efficacy occurred during the course of the study. Adverse events were reported by 62% of the patients.
Sumatriptan succinate (SMT) was a highly specific 5-HT1-receptor agonist. It showed high affinity only for 5-HT but no affinity for other neurotransmitter receptors such as muscarinic, dopamine D1, D2, adrenergic alpha 1, alpha 2, and beta. Furthermore, it was highly selective for 5-HT1B/1D-receptor and showed no affinity for 5-HT2 and 5-HT3 receptors. SMT contracted isolated cranial arteries such as basilar, midcerebral, temporal arteries and large arteries in the dura matter, but did not contract coronary, femoral, mesenteric and other arteries. Reflecting these results, SMT induced vasoconstriction of carotid artery, but produced practically no contractile responses in the other arteries mentioned above in anaesthetized animals. These pharmacological characteristics of SMT were different from those of ergot alkaloids, current anti-migraine drugs, which contracted coronary, femoral and other arteries as well. SMT inhibited neurotransmitter release, including CGRP, from trigeminal nerve terminals. Consequently protein extravasation induced by CGRP was inhibited and neurogenic inflammation could be suppressed. It was believed that SMT showed its anti-migraine activity through cranial vasoconstriction via 5-HT1B/1D receptors, since it did not show any analgesic activities. Its clinical efficacy on migraine and cluster headache had been already confirmed in about 100 western countries. Its efficacy was also shown by open trials and placebo controlled double blind tests in Japan.
Oral sumatriptan, which is a well tolerated, effective acute treatment for migraine, and is selectively available in different countries in 100 mg, 50 mg, and 25 mg tablets. The first large dose-ranging study compared the 100 mg dose to higher doses (200 mg and 300 mg) and found it to be just as efficacious and better tolerated. The first studies comparing the 100 mg dose to lower doses (25 mg and 50 mg) found them all to be similar in effectiveness and tolerability. However, a larger definitive study found that the 100 mg and 50 mg doses offered better efficacy than the 25 mg dose, whereas the 25 mg and 50 mg doses were better tolerated than the 100 mg dose. Thus the 50 mg dose appears to offer the best ratio of efficacy to tolerability. Many patients, though, prefer or require the 100 mg dose and tolerate it well. Allowed to select dosing themselves, patients tend to migrate to the 100 mg dose.
A 25-year-old woman (gravida 1, para 0) who had no history indicating the toxemia of pregnancy developed hypertension and severe throbbing headache after the delivery of her first child by the cesarean section. Generalized tonic-clonic seizure ensued 5 days after the delivery, after which she did not fully regain her consciousness. Her head T2-weighted and FLAIR MRIs showed areas of multiple high intensities in the basal ganglia and cerebral white matter. Her cerebral MRA revealed the segmental stenosis and irregular wall of the major vessels, in particular of the right MCA trunk. Three weeks later, these abnormalities in the neuroimages disappeared and she was free of any symptoms. The history disclosed that obstetricians had used methylergometrine maleate for uterine contraction after delivery and then sumatriptan for her throbbing headache. We speculate that these vasoconstrictive agents might have induced the postpartum cerebral angiopathy. Postpartum cerebral angiopathy may be distinct from reversible posterior leukoencephalopathy in that the abnormalities are not restricted to the posterior lobes and that the vascular changes are apparent on neuroimagings. However, this entity might have a common underlying physiology, which is the abnormally elevated blood pressure that occurs in the setting of early postpartum period. Caution should be exercised when vasoconstrictives are to be used in postpartum period.
A 65-year-old woman was referred with confusion, strange behaviour, sinus tachycardia, hypertension and hyperthermia. She had been taking sumatriptan and paroxetine and recovered completely after discontinuation of these agents. The diagnosis was 'serotonin syndrome', a result of overstimulation of 5-HT(1A) receptors in the raphe nuclei of the brainstem. It is a complication of the use of serotonergic agents and is associated with the rapid onset of mental, autonomic and neurological symptoms. Treatment consists of discontinuation of the suspected medication and, in severe cases, providing symptomatic relief. Given the frequent prescription of (combinations of) serotonergic agents, one should be aware of this complication.
Sumatriptan (CAS 103628-46-2, 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulphonamide++ +), a substance for treatment of acute migraine attacks, and its main metabolite are investigated by thinlayer chromatography (TLC), ultraviolet spectroscopy, and gas chromatography/mass spectrometry (GC/MS). The resulting analytical data (correlated hRf-values, UV solvent spectra, remission spectra, GC retention indices, and electron impact (EI) mass spectra) including an extraction procedure and different derivatization methods are presented. Their applicability is described for urine analysis.
Sumatriptan (SU), a specific 5-HT1D receptor agonist, was recently shown to be able to increase growth hormone (GH) levels in normals, but not in acromegalics, while no effect was seen on prolactine (PRL). SU is also able to produce an increase in GH response to growth hormone releasing hormone (GHRH) in prepubertal children. In this study we investigated whether SU administration influences GHRH-induced GH secretion in 8 acromegalics, and 6 age-matched normal volunteers, as a control group. We evaluated the effects of SU (6 mg s.c.) or placebo (PL) administration on GHRH (1 microgram/kg bw i.v.)-induced GH and PRL secretion. After SU priming the GH response to GHRH did not changed in acromegalics, but significantly decreased in controls, in comparison with that observed after PL plus GHRH. In acromegalics, no difference in GH peak was seen after SU plus GHRH and PL plus GHRH, nor was any difference seen in AUC between tests. In controls, no difference was seen in GH peaks, while SU priming significantly (P < 0.03) decreased the AUC 90-120 min of GH after GHRH administration. In acromegalics, SU did not change the slight GHRH-induced increase in PRL levels. Our study documents that 5-HT1 D receptors do not interfere with GHRH-stimulated GH secretion in acromegalic subjects. In normals, SU is able to decrease GH response to GHRH, thus confirming that 5-HT1D receptors are able to modulate GH secretion in normals.
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