Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The purpose of this study was to investigate the mechanism of nicotine-evoked relaxation of the guinea-pig isolated basilar artery and to study the effects of drugs associated with the aetiology or treatment of migraine on the nicotine response. 2. The guinea-pig isolated basilar artery, pre-contracted with prostaglandin F2alpha (PGF2alpha), in the presence of atropine (3 microM) and guanethidine (3 microM), relaxed on addition of nicotine (0.1 mM) in approximately 50% of preparations. The responses to nicotine were of short duration and blocked in preparations pre-treated for 10 min with capsaicin (1 microM) and are therefore probably a consequence of the stimulation of trigeminal C fibre terminals. 3. Responses to nicotine were reduced in the presence of 5-carboxamidotryptamine, 5-hydroxytryptamine and sumatriptan in that order of potency. This is consistent with a 5-HT1 receptor mechanism. These agonists evoked small additional contractions in vessels pre-contracted with PGF2alpha. 4. Indomethacin (0.3-10 microM), aspirin (10-30 microM), and nitro-L-arginine methyl ester (L-NAME, 0.1 mM) reduced nicotine-evoked relaxation of the basilar artery, suggesting the involvement of both nitric oxide and cyclo-oxygenase products in this response. 5. Progesterone (1 microM) markedly reduced the response to nicotine, a possible reflection of the ion channel blocking activity of high concentrations of this compound. 6. The guinea-pig basilar artery is a preparation in which the effects of drugs on responses to stimulation of trigeminal nerve terminals can be studied in vitro and may thus be of interest in assessing the actions of drugs used in treatment of headache.
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PMID:The inhibition of nicotine-evoked relaxation of the guinea-pig isolated basilar artery by some analgesic drugs and progesterone. 1019 81

We examined the effects of avitriptan, a 5-hydroxytryptamine 1-like (5HT1) receptor agonist for the treatment of migraine, in patients with medicated, controlled, mild to moderate hypertension relative to placebo and sumatriptan. The study was randomized, double-blinded, placebo-controlled, and 4-way crossover in design. Twenty patients (12M, 8F) participated. As required by protocol, all were stable on medications for mild to moderate hypertension, with a supine diastolic blood pressure of < 95 mmHg. Qualified subjects were randomized to receive oral administration of either 75 or 150 mg of avitriptan, 100 mg sumatriptan or placebo during the four treatment visits. Supine blood pressure and pulse rates were recorded up to 24 h after drug administration. Avitriptan 150 mg significantly increased peak diastolic and systolic blood pressure, and mean arterial pressure compared to placebo and sumatriptan 100 mg (p < 0.05). Only those hypertensive patients receiving medication for hypertension should receive anti-migraine medications, such as avitriptan, which are 5HT1-like receptor agonists.
Cephalalgia 1999 Mar
PMID:A double-blind, randomized, crossover assessment of blood pressure following administration of avitriptan, sumatriptan, or placebo to patients with mild to moderate hypertension. 1021 34

To identify potential migraine therapeutics, extracts of eighteen plants were screened to detect plant constituents affecting ADP induced platelet aggregation and [14C]5-hydroxytryptamine (5-HT) release. Extracts of the seven plants exhibiting significant inhibition of platelet function were reanalysed in the presence of polyvinyl pyrrolidone (PVP) to remove polyphenolic tannins that precipitate proteins. Two of these extracts no longer exhibited inhibition of platelet activity after removal of tannins. However, extracts of Crataegus monogyna, Ipomoea pes-caprae, Eremophila freelingii, Eremophila longifolia, and Asteromyrtus symphyocarpa still potently inhibited ADP induced human platelet [14C]5-HT release in vitro, with levels ranging from 62 to 95% inhibition. I. pes-caprae, and C. monogyna also caused significant inhibition of ADP induced platelet aggregation. All of these plants have been previously used as traditional headache treatments, except for C. monogyna which is used primarily for protective effects on the cardiovascular system. Further studies elucidating the compounds that are responsible for these anti-platelet effects are needed to determine their exact mechanism of action.
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PMID:Inhibition of platelet aggregation and 5-HT release by extracts of Australian plants used traditionally as headache treatments. 1066 75

Sumatriptan succinate (Imitrex) is a 5-HT (5-hydroxytryptamine) agonist used for relief of migraine symptoms. Some individuals experience short-lived side-effects, including heaviness of the limbs, chest heaviness and muscle aches and pains. The effects of this drug on skeletal muscle energy metabolism were studied during short submaximal isometric exercises. We studied ATP flux from anaerobic glycolysis (An Gly), the creatine kinase reaction (CK) and oxidative phosphorylation (Ox Phos) using 31P nuclear magnetic resonance spectroscopy (31P MRS) kinetic data collected during exercise. It was found that side-effects induced acutely by injection of 6 mg sumatriptan succinate s.c. were associated with reduced oxygen storage in peripheral skeletal muscle 5-20 min after injection as demonstrated by a transient reduction in mitochondrial function at end-exercise. These results suggest that mild vasoconstriction in peripheral skeletal muscle is associated with the action of sumatriptan and is likely to be the source of the side-effects experienced by some users. Migraine with aura patients were more susceptible to this effect than migraine without aura patients.
Cephalalgia 2000 Feb
PMID:Effects of the anti-migraine drug sumatriptan on muscle energy metabolism: relationship to side-effects. 1081 45

The question about the 5-hydroxytryptamine (5-HT)(1B-1D) receptors agonists, if the clinical efficacy in migraine attacks is linked with the action at the central level or at the peripheral one, is still unresolved. We evaluated the effects of zolmitriptan and sumatriptan on blink reflex in thirty migraine without aura patients during the attacks in order to assess the central action on the trigeminal system. Both drugs were effective in reducing headache severity compared to placebo. In the migraine attack an increased area of the R3 component on the pain side was observed; it was suppressed by zolmitriptan, which confirmed its action on the central trigeminal circuits, though the clinical relevance of this effect could be questioned.
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PMID:Zolmitriptan reverses blink reflex changes induced during the migraine attack in humans. 1089 8

The urinary excretion products of serotonin (5-hydroxytryptamine, 5HT) are 5-hydroxyindole-3-acetic acid (5HIAA) and 5-hydroxytryptophol (5HTOL), and the ratio of 5HTOL to 5HIAA is normally very low (< 0.01 ) in man. Intake of foods rich in 5HT (high amounts in banana, pineapple, and walnuts) induces a general increase in the output of 5HT metabolites, without affecting the 5HTOL/5HIAA ratio. In contrast, during metabolism of ethanol there is a shift in the catabolic pattern of 5HT, and the formation of 5HTOL increases appreciably at the expense of 5HIAA. Accordingly, the urinary 5HTOL/ 5HIAA ratio increases and does not recover to baseline levels until several hours after ethanol has been cleared from the body. When 10 healthy subjects ingested a moderate dose of ethanol (0.5 g/kg), the urinary 5HTOL/SHIAA ratio was increased approximately 70-fold on average at 4 h after intake. When the same amount of ethanol was ingested together with 3 bananas (approximately 10 mg 5HT), this ratio was increased approximately 100-fold at 4 h and still significantly higher than baseline levels at 24 h. Starting at 3-4 h after the combined intake of ethanol and banana, 7 subjects experienced one or more unpleasant symptoms (diarrhea, headache, and fatigue) which are associated with the 5HT system. The events were transient but typically lasted for several hours, and the duration correlated with the time period during which 5HTOL levels were raised. Intake of ethanol and banana separately produced much lower increases in 5HTOL output and caused no corresponding effects. This observation indicate that dietary 5HT intake together with even a moderate dose of ethanol can provoke unpleasant physiological symptoms. The symptoms may be attributed to the high concentration of 5HTOL.
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PMID:Dietary serotonin and alcohol combined may provoke adverse physiological symptoms due to 5-hydroxytryptophol. 1096 9

A 50-year-old fisherman was stung in his right hand by a Great Weever fish (Trachinus draco). The crew did not have sufficient medical knowledge to adequately treat him on board. Severe pain, oedema of the hand, fever, vomiting and syncope occurred. Treatment with antibiotics, on board, after disembarkation and later in hospital for six days reduced the severity of the symptoms. However, two years after the accident, the patient still suffered from a dysfunction of the right hand as well as extreme fatigue and intermittent joint complaints. The symptoms mostly commonly arising from a Weever fish sting are: severe pain, local erythema and oedema. Systemic symptoms may sometimes occur: headache, syncope, bradycardia, fever and hypotension. The symptoms of continuous joint pain and severe fatigue following a Weever sting have not been previously described. The Weever fish venom contains a mixture of biogenous amines, of which some are known: 5-hydroxytryptamine, epinephrine, norepinephrine and histamine. The venom's composition has yet to be fully elucidated. In the event of a Weever fish sting, the first aid which should be given is: clean the wound and immerse the affected part of the body for at least 30 minutes in water which is as hot as the victim can tolerate (40-45 degrees C). Persons at risk from Weever fish stings are bathers, especially from the Lesser Weever fish (Echiichthys vipera), and sea fishermen. General practitioners and first aiders in coastal areas as well as sea fishermen should be informed about the first aid to be given in the event of a Weever sting.
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PMID:[Chronic pain and impairment of function after a sting by the great weaver fish (Trachinus draco)]. 1137 1

Paroxetine is a potent and selective serotonin reuptake inhibitor (SSRI) with currently approved indications for the treatment of depression, obsessive-compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post traumatic stress disorder, premenstrual dysphoric disorder and chronic headache. Paroxetine, a phenylpiperidine derivative, is the most potent inhibitor of the reuptake of serotonin (5-hydroxytryptamine, 5-HT) of all the currently available antidepressants including the class of SSRIs. It is a very weak inhibitor of norepinephrine (NE) uptake but it is still more potent at this site than the other SSRIs. The selectivity of paroxetine, i.e., the ratio of inhibition of uptake of norepinephrine to serotonin (NE/5-HT) is amongst the highest of the SSRIs. Paroxetine has little affinity for catecholaminergic, dopaminergic or histaminergic systems and by comparison with tricyclic antidepressants (TCAs) has, therefore, a reduced propensity to cause central and autonomic side effects. Paroxetine exhibits some affinity for the muscarinic cholinergic receptor but much less than the TCAs. In addition, the adaptive changes of somatodendritic (5-HT(1A)) and terminal (5-HT(1B/1D)) autoreceptors observed with paroxetine are different to those observed with TCAs; it also inhibits nitric oxide synthase. It is both a substrate and an inhibitor of cytochrome isoenzyme P450 2D6. Paroxetine is well absorbed orally and undergoes extensive first pass metabolism that is partially saturable. Its metabolites are pharmacologically inactive in vivo. Steady state levels are achieved after 4-14 days and an elimination half-life of 21 h is consistent with once-daily dosing. There is wide inter-individual variation in the pharmacokinetics of paroxetine in adults as well as in the young and the elderly with higher plasma concentrations and slower elimination noted in the latter. Elimination is also reduced in severe renal and hepatic impairment. Serious adverse events are, however, extremely rare even in overdose. In summary, paroxetine is well tolerated and effective in the treatment of both depressive and anxiety disorders across the age range.
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PMID:Paroxetine: a review. 1142 May 71

Extracts of Australian plants were screened to detect constituents affecting adenosine di-phosphate (ADP) induced platelet aggregation and [14C]5-hydroxytryptamine (5-HT) release. Extracts of four tested plants including, Eremophila gilesii, Erythrina vespertilio, Cymbopogon ambiguus, and Santalum acuminatum, were found to cause significant inhibition of platelet 5-HT release. Inhibition levels ranged from 56-98%, and was not due to the non-specific effects of protein binding tannins. These extracts, and those we have previously identified as being active, were examined further to determine if they affect epinephrine (EPN), arachidonic acid (A.A) or collagen stimulated platelet aggregation and 5-HT release. Among those extracts investigated, we found that both the methanolic extract of E. vespertilio and the dichloromethane (DCM) extract of C. ambiguus were most potent and caused significant inhibition of platelet activation induced by EPN, A.A and to a lesser extent by collagen. Inhibition of ADP induced platelet 5-HT release by both of these extracts, was dose-dependent, with IC50 values for E. vespertilio and C. ambiguus estimated to be 20.4 microl (1.855 mg/ml) and 8.34 microl (0.758 mg/ml), respectively. Overall, C. ambiguus exhibited most activity and also caused dose-dependent inhibition of A.A induced platelet activation. These results indicate that inhibition may occur specifically at a site within the A.A pathway, and suggest the presence of a cyclo-oxygenase inhibitor. Both E. vespertilio and C. ambiguus are reported to be traditional headache treatments, with the present study providing evidence that they affect 5-HT release.
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PMID:Modulation of in vitro platelet 5-HT release by species of Erythrina and Cymbopogon. 1166 43

Serotonin (5-hydroxytryptamine) is a potent vasoconstrictor amine. The authors report three patients who developed thunderclap headache, reversible cerebral arterial vasoconstriction, and ischemic strokes (i.e., the Call-Fleming syndrome). The only cause for vasoconstriction was recent exposure to serotonergic drugs in all patients, and to pseudoephedrine in one patient. These cases, and the literature, suggest that the use of serotonin-enhancing drugs can precipitate a cerebrovascular syndrome due to reversible, multifocal arterial narrowing.
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PMID:Cerebral vasoconstriction and stroke after use of serotonergic drugs. 1474 13


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