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PubMedDate not supplied

Renal papillary necrosis following emergency department treatment of migraine.

New medications have lessened the need for narcotic medications in the acute treatment of migraine. Some of these new medications include parenteral dihydroergotamine (DHE), sumatriptan, and ketorolac. Treatment failures still occur, though, and some cases necessitate adding a second agent to one that has been ineffective. We report a case of a 46-year-old man who suffered renal papillary necrosis 12 days after receiving parenteral DHE, sumatriptan, and ketorolac for treatment of a severe migraine headache. There were no signs of an adverse drug reaction at the time of his emergency department visit. The case illustrates a potential hazard of this combination in the acute treatment of migraine.

Analgesics, Non-Narcotic↗
PubMed1994

5-HT1D receptor type is involved in stimulation of cell proliferation by serotonin in human small cell lung carcinoma.

Serotonin (5-hydroxytryptamine, 5-HT), a neurotransmitter and vasoactive agent, is contained in two small cell lung carcinoma cell lines GLC8 and NCI-N-592 and is released in the culture medium. It also stimulates DNA synthesis in the same cell lines. In GLC8 cells this mitogenic effect is not counteracted by ketanserin, ICS 205-930 and GR 113-808 which are antagonists of the 5-HT2, 5-HT3 and 5-HT4 receptors, respectively. On the contrary, the antagonists metergoline, methysergide, SDZ 21-009 and methiothepin inhibit the 5-HT-stimulated incorporation of [3H]thymidine in GLC8 cells. The 5-HT1D agonist sumatriptan is capable of mimicking 5-HT action on cell proliferation. Both sumatriptan and 5-HT inhibit adenylate cyclase activity at doses which correlate with the mitogenic effect. We conclude that a 5-HT1D receptor type contributes to the mitogenic effect of 5-HT in GLC8 cells. This is the first demonstration of an involvement of the 5-HT1D receptor type in human cell proliferation. The design of specific antagonists for this type of receptor might be useful for the growth control of this very aggressive tumor.

Adenylyl Cyclase Inhibitors↗
PubMed2005

Accessing a new medication in Germany: a novel approach to assess a health insurance-related barrier.

PURPOSE: Knowledge of the existence, position, and magnitude of barriers to equitable healthcare is an important consideration in shaping healthcare policies. METHODS: The authors developed a novel three-dimensional person-time-related hurdle model and followed a cohort of 7358 statutorily (SHI) and 457 privately health insured (PHI) patients with migraine headaches at 377 primary-care practices (MediPlus, IMS Health) in the second to fourth year of the HealthCare Structural Reform Act in Germany. RESULTS: For SHI compared with PHI migraine patients, there was a hurdle to receiving sumatriptan at all (2.4-fold lower hazard, 95% confidence interval, 1.8-3.2). Among patients who received sumatriptan, frequency and intensity of use differed only minimally between SHI and PHI patients. CONCLUSIONS: These findings have implications for healthcare researchers and healthcare policies. The framework extends traditional hurdle models and can serve as a model for quantifying barriers to receipt of services under different funding policies.

Adolescent↗
PubMed2004

Evidence for serotonin influencing the thalamic infiltration of mast cells in rat.

Serotonin (5-HT) is involved in neuroimmunomodulation. We analyzed the effects of sumatriptan, a 5-HT(1B/1D) receptor agonist, and ondansetron, a 5-HT(3) receptor antagonist, on thalamic mast cell (TMC) population, the only immunocytes known to infiltrate the brain in physiological conditions. Only sumatriptan was effective, significantly increasing TMC numbers versus controls, and especially those containing 5-HT. 5-HT(1B) receptors are concentrated in the median eminence on non-serotonergic axonal endings, probably hypothalamic terminal fibers, involved in hypothalamic-pituitary neuroendocrine modulating processes. TMC variations could reflect serotonergic actions on these fibers. TMCs would thus be cellular interfaces mediating immune action in the nervous system in relation with the hormonal status of the organism.

Animals↗
PubMed2005

Non-human primate SPECT model for determining cerebral perfusion effects of cerebrovasoactive drugs acting via multiple modes of pharmacological action.

Increasing clinical and experimental evidence implicate cerebral hypoperfusion during increased ageing and points to chronic cerebrovascular ischemia as a vital component of the neuropathological progression of dementia. In vivo cerebral perfusion animal models can greatly contribute to the evaluation of drugs and to the screening of drug interactions. This study describes a baboon Papio ursinus model under anaesthesia, for in vivo cerebral blood flow (CBF) determinations, using Single Photon Emission Computed Tomography (SPECT) following the split-dose method with 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO). Perfusion studies with acetazolamide as intervention clearly showed that the non-human primate model under aneasthesia is sufficiently sensitive to serve in the evaluation of other cerebrovasoactive drugs for induced perfusion changes with significant increases of the R-value (+40%) for comparative measurement when compared to the control value (2.53+/-0.15 vs. 1.79+/-0.13). These findings stimulated investigations of several drugs, i.e. pentifylline (phosphodiesterase inhibitor); nimodipine (calcium channel blocker); sumatriptan (serotonin receptor agonist) and nicotinic acid (vasodilator) for CBF effects. Increases in the cerebral perfusion in some cases more than +30% for nimodipine (2.51+/-0.14 vs. 1.79+/-0.13), acetazolamide and +29% for the combination of pentifylline and nicotinic acid (2.31+/-0.19 vs. 1.79+/-0.13) were observed. Drug interaction studies revealed an attenuation of increased CBF due to nimodipine, with sumatriptan (-25%) and acetazolamide (+22%) in combination with nimodipine. Drug interactions with clinical implications may result during simultaneous use of cerebrovasoactive drugs in managing patients with cerebrovascular disorders. This study further showed that the CBF non-human primate model under anaesthesia is useful for the investigation of vasoactive drugs acting via various pharmacological modes of action.

Animals↗
PubMed2004

Hippocampal 5-hydroxytryptamine receptors: abnormalities in postmortem brain from schizophrenic subjects.

There is strong evidence that hippocampal 5-hydroxytryptamine (5-HT) systems are affected in schizophrenia and hence we have studied a number of markers of the 5-HT system in hippocampi from subjects with schizophrenia. Using in situ radioligand binding with autoradiography we measured [(3)H]proplyamino-8-hydroxy-1,2,3,4-tetrahydronapthalene, [(3)H]ketanserin and [(3)H]sumatriptan binding in hippocampi from 20 schizophrenic and 20 control subjects. There were significant decreases in the density of [(3)H]ketanserin binding to the 5-HT(2A) receptor (5-HT(2A)R) in the Cornu Ammonis (CA) 3 (p=0.006), CA 1 (stratum radiatum p=0.02; pyramidal layer p=0.0008) and subiculum (pyramidal layer p=0.0004), as well as methiothepin-insensitive [(3)H]sumatriptan binding to the 5-HT(1F)R in the CA 1 (p=0.016), stratum radiatum/lacunosum moleculare (p=0.04) and subiculum (p=0.015) from subjects with schizophrenia. There were no differences in the densities of 5-HT(1A)R, 5-HT(1D)R or 5-HT(4)R in hippocampi from subjects with schizophrenia. These data support the hypothesis that regionally specific reductions in the density of the 5-HT(2A)R and 5-HT(1F)R are a component of the pathological processes underlying schizophrenia.

Adult↗
PubMed1997

Chronic paroxetine desensitises 5-HT1D but not 5-HT1B autoreceptors in rat lateral geniculate nucleus.

The present study examined the effect of chronic paroxetine (10 mg/kg p.o., 21 days) on the 5-HT1B and 5-HT1D autoreceptors controlling 5-HT efflux in slices of rat ventrolateral geniculate nucleus. Electrically stimulated 5-HT efflux (10 pulses, 200 Hz, 0.1 ms, 10 mA) was measured using fast cyclic voltammetry. Peak 5-HT efflux was greater (P < 0.01) after chronic paroxetine (22.2 +/- 1.4 nM, mean +/- S.E.M.) than water (15.8 +/- 1.4 nM). 5-HT efflux was inhibited by CP 93129 (1 nM-10 microM) and sumatriptan (1 nM-1 microM), agonists at 5-HT1B and 5-HT1D receptors, respectively. Chronic paroxetine did not affect the sensitivity of the 5-HT1B autoreceptor but shifted the sumatriptan concentration-response curve to the right (P < 0.05). These data suggest that chronic paroxetine increases evoked 5-HT efflux. This may be the result of desensitisation of 5-HT1D but not 5-HT1B autoreceptors.

Animals↗
PubMed2000

Neurogenic vasodilation in rabbit basilar isolated artery: involvement of calcitonin-gene related peptide.

Neurogenic vasodilation in cranial arteries may be an important mechanism in the pathogenesis of migraine headache. We describe a novel, in vitro assay to characterise neurogenic vasodilator responses in endothelium-denuded segments of rabbit isolated basilar artery, with particular focus on calcitonin-gene related peptide (CGRP). In arterial segments precontracted with prostaglandin F(2alpha), relaxations evoked by exogenously applied alphaCGRP (EC(50)=2.9 nM) were inhibited by alphaCGRP-(8-37) (pA(2)=6.49) or by desensitisation resulting from prior exposure to alphaCGRP. Relaxations evoked by exogenously applied vasoactive intestinal polypeptide (VIP) (EC(50)=2.5 nM) were inhibited by VIP-(7-28) 1 microM. The 5-HT(1) receptor agonists L-771,331 ((3S)-3[N-(S)-alpha-methylbenzyl]aminomethyl-(S)-1-[2-(5-(2-oxo-1, 3-oxazolidin-4-ylmethyl)-1H-indol-3-yl)ethyl]pyrrolidine) and sumatriptan exerted contractile effects (EC(50)=293 and 95 nM, respectively). In neurogenic experiments, vasodilation evoked by electrical field stimulation was markedly attenuated by pre-treatment with capsaicin (10 microM) or by prior CGRP receptor desensitisation and to a lesser extent by pre-treatment with VIP-(7-28) 1 microM. L-771,331 (100 nM) exerted a weak inhibitory effect, marked only by a short reduction in the recovery time (post-electrical stimulation) and sumatriptan (30 nM) had no effect. The neurogenic response was potentiated by alphaCGRP-(8-37) 1 microM (reversible on wash-out). Short application (5-10 min) of capsaicin (10 microM) produced vasodilation that was inhibited by alphaCGRP-(8-37) 1 microM. These data suggest that electrically evoked neurogenic vasodilation in rabbit basilar artery has a large component resulting from the release of sensory neuropeptides in particular CGRP and a smaller component involving the release of VIP.

Animals↗
PubMed2000

Effects of SL 65.0472, a novel 5-HT receptor antagonist, on 5-HT receptor mediated vascular contraction.

5-hydroxytryptamine (5-HT) contracts vascular smooth muscle and pharmacological and molecular biological data suggest that these effects are mediated primarily by stimulation of 5-HT(1B) and 5-HT(2A) receptor subtypes. We have studied the properties of 7-fluoro-2-oxo-4-[2-[4-(thieno[3,2-c] pyridin-4-yl) piperazin-1-yl] ethyl]-1,2-dihydroquinoline-1-acetamide (SL 65.0472 ), a novel 5-HT receptor antagonist, in isolated vascular preparations contracted by 5-HT or sumatriptan. In canine isolated saphenous vein strips (putatively 5-HT(1B)-mediated contraction), SL 65.0472 antagonised sumatriptan-induced contractions in a competitive manner (pA(2) 8. 17+/-0.36). 5-HT contracts rabbit aorta by stimulation of 5-HT(2A) receptors. SL 65.0472 displaced the 5-HT concentration response curve in rabbit aorta rightwards with a significant reduction in maximum. The apparent pK(B) value was 8.58+/-0.18. 5-HT-induced contractions of human coronary arteries are mediated by a mixed population of 5-HT(1B) and 5-HT(2A) receptors. SL 65.0472 produced rightward parallel shifts of the 5-HT concentration response curves in all tissues studied (pA(2) 8.8+/-0.14, n=7). In conclusion, SL 65. 0472 is a potent antagonist of vascular smooth muscle contraction in vitro mediated by 5-HT receptor stimulation.

Animals↗
PubMed2000

In vivo analysis of adrenergic and serotoninergic constrictions of the rabbit saphenous vein.

We aimed to develop a model to study in vivo the rabbit saphenous vein pharmacology and to investigate constrictions mediated by adrenoceptor and 5-HT receptor subtypes. We used the technique of high precision ultrasonic echo-tracking for direct measurement of saphenous vein diameters in pentobarbital anesthetized rabbits. Saphenous vein constrictions induced in rabbits by the alpha(1)-adrenoceptor agonist L-phenylephrine and the 5-HT(1B) receptor agonist sumatriptan were comparable with those induced in dogs but those induced by the 5-HT(1B) and 5-HT(7) receptor agonist 5-carboxamidotryptamine failed to appear in dogs. Dose-related constrictions of rabbit veins were obtained with L-phenylephrine and the alpha(2)-adrenoceptor agonist dexmedetomidine. Frequency-related constrictions of rabbit veins induced by nerve stimulation were partially inhibited by an alpha(1)-adrenoceptor or a postsynaptic alpha(2)-adrenoceptor antagonist (prazosin and SKF 104,078) but not affected by the pre- and post-synaptic alpha(2)-adrenoceptor antagonists BRL 44408 or rauwolscine. Constrictions of rabbit veins to sumatriptan and 5-CT were inhibited by GR 127935 and those induced by quipazine, a 5-HT(2) receptor agonist were prevented by ritanserin. The initial constrictions induced by 5-CT were followed by dilatations which were inhibited by the 5-HT(7) receptor antagonist mesulergine. These data indicate that rabbit saphenous veins, in vivo and at rest, respond to activation of 5-HT(1B) and 5-HT(2) receptors, alpha(1)- and alpha(2)-adrenoceptors and nerve stimulation; the dilator effect mediated by 5-HT(7) receptor activation was also detected. The data validate a new animal model to study superficial vein reactivity and its pharmacological sensitivity.

Adrenergic Agents↗
PubMed1998

The canine external carotid vasoconstrictor 5-HT1 receptor: blockade by 5-HT1B (SB224289), but not by 5-HT1D (BRL15572) receptor antagonists.

In vagosympathectomised dogs pre-treated intravenously (i.v.) with mesulergine (300 microg/kg), 1-min intracarotid (i.c.) infusions of 5-hydroxytryptamine (5-HT; 0.3-30 microg/min) and sumatriptan (1-30 microg/min) dose-dependently decreased external carotid blood flow, without affecting mean blood pressure or heart rate. Treatment with the selective 5-HT1B receptor antagonist SB224289 (2,3,6,7-tetrahydro-1'-methyl-5-[2'-methyl-4'(5-methyl-1,2,4-oxadiazo l-3-yl) biphenyl-4-carbonyl]furo[2,3f]indole-3-spiro-4'-piperidine hydrochloride; 30-300 microg/kg, i.v.) produced a potent, specific and dose-dependent blockade of this response, whereas the selective 5-HT1D receptor antagonist BRL15572 (1-(3-chlorophenyl)-4-[3,3-diphenyl(2-(S,R) hydroxypropanyl)piperazine]hydrochloride; 30-300 microg/kg, i.v.) was ineffective. It is concluded that mainly 5-HT1B, but not 5-HT1D receptors mediate the canine external carotid vasoconstriction by 5-HT and sumatriptan.

Anesthesia↗
PubMed1999

Characterisation of 5-HT receptors in human coronary arteries by molecular and pharmacological techniques.

5-Hydroxytryptamine (5-HT) can produce both vasoconstrictor and vasorelaxant effects in human coronary arteries and the response to 5-HT can be influenced by the presence of disease. The aim of the present study was to elucidate the 5-HT receptor subtypes responsible for mediating 5-HT-evoked contraction of human coronary arteries using pharmacological, molecular and immunocytochemical approaches. Normal human coronary arteries, with intact endothelium, were mounted in tissue baths, and the vascular responses to 5-HT and 5-HT receptor agonists were studied. The effects of 5-HT1 and 5-HT2 receptor antagonists on these responses were also studied. Expression of messenger ribonucleic acid (mRNA) encoding different 5-HT receptors in human coronary arteries, atrium, ventricle wall and epicardium was determined using reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis. The expression of 5-HT1B or 5-HT1D receptor protein was studied using subtype selective antibodies and standard immunocytochemical techniques. The rank order of 5-HT receptor agonist potency in causing vasoconstriction was 5-carboxamido tryptamine, (5-CT) > zolmitriptan = BW183C91 (N10-desmethyl zolmitriptan) = alpha-methyl-5-hydroxytryptamine (alpha-CH3-5-HT) = 5-HT = sumatriptan > 2-methyl-5-hydroxytryptamine (2-CH3-5-HT) = 8-hydroxy-DPAT (8-OH-DPAT). Alpha-CH3-5-HT, 5-CT, 5-HT, zolmitriptan and BW 183C91 were significantly more potent (approximately 3-fold) than sumatriptan and 2-CH3-5-HT, which in turn were more potent than 8-OH-DPAT. Ketanserin and methiothepin (5-HT2 and 5-HT1 receptor antagonists, respectively) caused parallel rightward shifts of the concentration-effect curves to alpha-CH3-5-HT or 5-CT, respectively, without changing the maximum contractile response. In human coronary arteries, atrium. ventricle and epicardium. RT-PCR products corresponding to the human 5-HT2A, 5-HT1B and 5-HT1F receptors were expressed in high levels, mRNAs coding for 5-HT7, 5-HT1A and 5-HT1D receptors were only weakly expressed. No 5-HT1F receptor mRNA was detected. In coronary arteries there was a differential expression of 5-HT1B versus 5-HT1D receptor mRNAs, with 5-HT1B mRNAs being found in greater abundance. Dense 5-HT1B-immunoreactivity was detected on smooth muscle layer within coronary artery, however, 5-HT1D-immunoreactivity was not detected. It is concluded that 5-HT-evoked contraction of human coronary arteries is most probably mediated via the activation of both 5-HT1B and 5-HT2A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1999

Pharmacological aspects of experimental headache models in relation to acute antimigraine therapy.

The last decade has witnessed a tremendous progress in the acute therapy of migraine, with sumatriptan, belonging to a new class of drugs, now known as 5-HT(1B/1D/1F) receptor agonists, leading the way. The undoubted success of sumatriptan stimulated the development of new triptans as well as other suitable pharmacological tools and experimental models to probe into complex migraine mechanisms. In this review, we discuss the main experimental models for migraine, against the background of the disease pathophysiology and 5-HT receptors considered most important for migraine therapy. We believe that the use of these migraine models will provide even better treatment for migraine patients in the next millennium.

Animals↗
PubMed1998

Role of impaired gastric accommodation to a meal in functional dyspepsia.

BACKGROUND & AIMS: Impaired accommodation of the proximal stomach to a meal has been reported in functional dyspepsia, but its relevance to symptoms is unclear. The aim of this study was to test the hypothesis that impaired gastric accommodation causes early satiety. METHODS: A gastric barostat was used to study postprandial fundus relaxation in 35 healthy subjects and 40 patients with functional dyspepsia. Gastric emptying, Helicobacter pylori status, sensitivity to gastric distention, and a dyspepsia symptom score were obtained from all patients. In addition, the effect of sumatriptan, a fundus-relaxing 5-hydroxytryptamine1 agonist, on gastric accommodation and on early satiety in dyspeptic patients was studied. RESULTS: Impaired gastric accommodation to a meal was found in 40% of the patients. In univariate analysis, this was associated with early satiety and weight loss but not with hypersensitivity to gastric distention, presence of H. pylori, or delayed gastric emptying. In a multivariate analysis, only early satiety was associated with impaired gastric accommodation. Sumatriptan restored gastric accommodation, thereby significantly improving meal-induced satiety. CONCLUSIONS: Impaired relaxation of the proximal stomach to a meal is present in a high proportion of patients with functional dyspepsia. It is associated with symptoms of early satiety. Restoring gastric accommodation with a fundus-relaxing drug improves early satiety.

Adult↗
PubMedDate not supplied

New insights into the molecular actions of serotonergic antimigraine drugs.

Migraine is a painful and debilitating neurological disorder that affects approximately 10% of the adult population in Western countries. Sensitization and activation of the trigeminal ganglia nerves that innervate the meningeal blood vessels is believed to play an important role in the initiation and maintenance of migraine pain. In this capacity, release of the neuropeptide calcitonin gene-related peptide (CGRP) and the resultant neurogenic inflammation is thought to underlie the pathophysiology of migraine. Largely due to the success of the serotonin Type 1 migraine drugs such as sumatriptan, migraine pathology and therapy has become a focus of intensive clinical and physiological research during the past decade. The effectiveness of these drugs is thought to be due to their ability to block the stimulated secretion of neuropeptides from trigeminal nerves to break the vicious nociceptive cycle of migraine. A component of this nociceptive cycle involves activation of mitogen-activated protein kinase signaling pathways. Indeed, activation of mitogen-activated protein kinase pathways can increase CGRP neuropeptide synthesis and secretion. Recently, the serotonin Type 1 agonists have been shown to cause a prolonged increase in intracellular Ca(2+) in trigeminal ganglia neurons and an increased phosphatase activity that can repress stimulated CGRP secretion and transcription. Identification of molecular signaling events in migraine pathology and therapy has provided new insight into the pharmacology and signaling mechanisms of sumatriptan and related drugs, and may provide the foundation for development of novel treatments for migraine.

Calcitonin Gene-Related Peptide↗
PubMed1998

A fluorescence-based method for assessing dural protein extravasation induced by trigeminal ganglion stimulation.

Neurogenic dural inflammation has been proposed as a source of pain during migraine. Unilateral electrical stimulation of the trigeminal ganglion causes the ipsilateral release of inflammatory neuropeptides and subsequent dural plasma protein extravasation, a component of neurogenic inflammation. We measured the amount of protein leaking into the dural tissue of guinea pigs following trigeminal ganglion stimulation by exploiting the complexation reaction of endogenous proteins with the fluorescent dye Evans Blue, instead of utilizing exogenous radiolabeled albumin as commonly done in the literature. The amount of Evans Blue trapped in dural tissue following electrical stimulation of the trigeminal ganglion was measured using a fluorescence microscope equipped with a spectrophotometer. This method utilized multiple measurements on each dura sample which resulted in very precise values using a small number of animals per point (n = 3). Sumatriptan and CP-122,288 were found to dose-dependently prevent neurogenic dural extravasation. The potencies of CP-122,288 and sumatriptan were found to be similar to those reported in the literature when similar experimental protocols were used.

Animals↗
PubMed2000

Effect of chronic paroxetine treatment on 5-HT1B and 5-HT1D autoreceptors in rat dorsal raphe nucleus.

This study reports the effect of chronic paroxetine (10 mg/kg p.o., 21 days) on 5-HT1B and 5-HT1D autoreceptors controlling stimulated 5-HT efflux in slices of rat dorsal raphe nucleus. Electrically evoked 5-HT (10 pulses, 200 Hz, 0.1 ms, 10 mA) was measured using fast cyclic voltammetry. 5-HT efflux was inhibited by CP 93129 (10 nM-10 microM) and by sumatriptan (1 nM-1 microM) agonists at 5-HT1B and 5-HT1D receptors, respectively. Chronic paroxetine did not, initially, appear to alter the sensitivity of the 5-HT1B autoreceptors to CP 93129. However, when constructed in the presence of WAY 100635 (10 nM) the selective and silent 5-HT1A antagonist, there was a significant (P < 0.001) rightward shift of the CP 93129 concentration-response curve in the paroxetine-treated rats but not in the controls, implying a desensitisation of the 5-HT1B autoreceptor by paroxetine. Chronic paroxetine did not affect the sumatriptan concentration-response curve, even with WAY 100635 present, implying that there was no (de)sensitisation of the 5-HT1D autoreceptor. These data suggest that chronic paroxetine treatment may desensitise 5-HT1B autoreceptors in the dorsal raphe nucleus but that this effect is unmasked only when the dominant 5-HT1A autoreceptor control is antagonised.

Animals↗
PubMed2001

[Treatment of cluster headache].

INTRODUCTION: The cluster headache (CH) is one of the most severe types of head pain. It is a typical example of a periodic disease and the International Headache Society classification recognizes two forms of this disease: episodic and chronic CH. Its prevalence is about 0.1 to 0.4% in the general population. CURRENT KNOWLEDGE AND KEY POINTS PATHOPHYSIOLOGY: A global hypothesis is still lacking to explain the pain, the vasodilation, the autonomic features (ipsilateral lacrimation, conjunctiva injection, rhinorrhea, partial Horner syndrome, etc.) and the periodicity of the CH. Pain and vasodilation seem secondary to an activation of the trigeminal vascular system and the periodicity of the attacks is thought to be due to a dysfunction of hypothalamic biologic clock mechanisms. Treatment of acute CH attacks. The most effective agents are oxygen inhalation and subcutaneous sumatriptan, a 5HT1B and D receptor agonist which has vasoconstrictor and anti-neurogenic inflammation properties by blocking the release from the trigeminal-sensitive fibers of neuropeptides such as CGRP and substance P. With subcutaneous sumatriptan, headache relief is very rapid, within 5 to 10 min. Prophylactic treatment of CH: The number of attacks per day varies from one to three, but some patients can have four to eight per day and acute treatments fail to provide sufficient relief or give rise to side-effects. Several different regimens have been proven effective. FUTURE PROSPECTS AND PROJECTS: Contraindications and side-effects of the drugs limit the choice of the prophylactic treatment: corticosteroids in a tapering course, verapamil and methysergide are the most useful treatments of the episodic form. Lithium carbonate is more effective for the chronic stage of CH, but side-effects are often troublesome. Numerous other medications have been used for prophylaxis: valproate, capsaicin, beta-blockers. Unfortunately, double-blind studies are often lacking and are difficult to realize due to spontaneous variable remission of episodic CH. When adequate trials of drug therapies show a total resistance to the treatments, surgery may be considered. Radiofrequency trigeminal rhizotomy is the treatment of choice with 70% of beneficial effects. Risks and complications have to be discussed in balance with the benefit of the different surgical procedures.

Anti-Inflammatory Agents↗