Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043352 (xerostomia)
 4,250 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The demonstration that long-term administration of relatively low doses of clonidine decreased the responsiveness of blood vessels to vasodilator and vasoconstrictor drugs in animals led to its investigation in the prevention of migraine in man. Results of placebo-controlled and open therapeutic trials have shown that clonidine in low dosages (75 to 150 mug daily) is useful in preventing migraine headaches in about 30%-50% of patients. A 50% or greater reduction in headache frequency or headache indices has been reported in 40% of patients in controlled and open studies. Thus clonidine, like other drugs used in the interval therapy of migraine, can be expected to be effective in only a proportion of patients. Although clonidine has not been compared directly with other drugs used in the prophylactic treatment of migraine, the general clinical impression is that it is less effective then pizotifen or methysergide. Because it is relatively well tolerated at dosages of 75 to 150 mug daily it is worthy of a trial, particularly in patients considered to need prophylactic migraine therapy for the first time, and when migraine occurs in association with hypertension. At the dosages used in migraine prophylaxis, which are almost invariably lower than used in hypertension, clonidine does not cause hypotension and can be used in patients with cardiovascular disease. The principal side-effects are drowsiness and dry mouth which tend to diminish as treatment continues.
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PMID:Low-dose clonidine: a review of its therapeutic efficacy in migraine prophylaxis. 120 7

Flupirtine is a novel non-opiate centrally acting analgesic agent with muscle relaxant properties, advocated for use in a number of pain states. Preliminary evidence suggests that flupirtine 100 to 200mg orally or 150mg rectally 3 to 4 times daily (maximum daily dose 600mg) is more effective than placebo in relieving moderate acute pain of various types. For the relief of pain due to surgery, traumatic injury, dental procedures, headache/migraine and abdominal spasms, flupirtine has proved at least as effective as the opiate analgesics codeine, dihydrocodeine and pentazocine, the nonsteroidal anti-inflammatory agents suprofen, diclofenac and ketoprofen, as well as dipyrone and paracetamol (acetaminophen). Although evidence to support a role in the treatment of chronic pain is limited, flupirtine has been found as effective as pentazocine in short term trials of patients with muscular or neuralgiform pain, dysmenorrhoea, soft tissue rheumatism or cancer pain. The safety profile of flupirtine has not yet been fully established, although initial evidence suggests that adverse reactions, while frequent, are usually minor in nature. The most common reactions are drowsiness, dizziness, dry mouth and various gastrointestinal complaints. In comparison with opiate drugs, flupirtine appears to produce fewer central nervous system effects, no respiratory or cardiovascular depression, and no overt tolerance or physical dependence on prolonged administration. If these initially favourable results are confirmed in larger long term trials, then flupirtine would appear to represent an effective analgesic for the relief of moderate pain, particularly that of musculoskeletal origin.
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PMID:Flupirtine. A review of its pharmacological properties, and therapeutic efficacy in pain states. 768 75

The prophylactic value of a daily dose of 10 mg flunarizine, a calcium antagonist, was analysed in 100 migraineurs during 4-month in an open study. Ninety-three patients completed the full 16-week course of therapy, and seven patients presented important adverse reactions requiring discontinuation of the drug. However, the seven patients who dropped out during flunarizine treatment were not considered in the analysis. Side-effects included weight gain, sleepiness, humor depression, paresthesias and dry mouth. Eighty-one patients experienced abolition or significant reduction in headache incidence and/or severity. We conclude that flunarizine may be an effective drug in migraine prophylaxis.
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PMID:[Prophylactic treatment of migraine: a prospective open study on 100 patients]. 821 27

MK-462 is a potent, selective 5HT1D receptor agonist which may be useful in treating acute migraine. We conducted a double-blind placebo-controlled inpatient study to assess the preliminary efficacy and safety of oral doses of MK-462 20 mg (n = 8) and 40 mg (n = 36) vs placebo (n = 21), administered to 65 male and post-menopausal female migraine patients aged 22-51 with moderate or severe migraine headache. Headache severity and functional disability were measured at 0.5, 1, 1.5, and 2 h post-dose. The 20 mg dose was well tolerated and 4/8 patients obtained relief in headache severity at the 2 h time point. The 40 mg dose was well tolerated and was significantly (p < 0.05) superior to placebo at the 1.5 and 2 h time points (with 27/36 or 75% obtaining relief at 2 h compared to 7/21 or 33% for placebo). Adverse events occurred in 50% of patients on 20 mg MK-462, 72% of those on 40 mg MK-462, and in 52% of placebo-treated subjects. The most common adverse events associated with MK-462 were drowsiness (20 mg 12%; 40 mg 44%; placebo 24%), dry mouth (40 mg 36%; placebo 19%), and lightheadedness/dizziness (40 mg 17%; placebo 10%). Based on these preliminary results, MK-462 appears worthy of continued study for the treatment of acute migraine.
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PMID:Pilot study of MK-462 in migraine. 866 77

Zolmitriptan (Zomig, formerly 311C90) at doses of 0.5-50 mg was administered to 316 unique volunteers in clinical pharmacology studies and 2,750 unique patients in eight clinical studies of acute migraine treatment. Overall, subjects received almost 50,000 doses; 97% of exposures were at doses > or = 2.5 mg. In the clinical pharmacology studies, the overall incidence of subject exposures experiencing at least one adverse event was 52% with zolmitriptan 2.5 mg (28% with placebo). In placebo-controlled studies, the overall incidence of patients with at least one adverse event was dose-dependent for zolmitriptan over the 1-15 mg dose range, e.g. 42% and 46% with 1 and 2.5 mg, respectively and 58% with 5 mg (29% with placebo). Only four serious adverse events attributable to zolmitriptan were reported. In a long-term study, during which 2,058 outpatients treated a total of 31,579 migraine attacks with either one or two zolmitriptan 5 mg doses over a period of up to 1 year, the number of attacks associated with at least one adverse event was similar after one (26%) and two (24%) doses. The majority (59%) of the adverse events reported in this study (59%) occurred within 2 h of dosing, were predominantly mild (59%) or moderate (35%) in intensity, of < or = 4 h duration (58%), required no further action (94%). In placebo-controlled studies, the percentage of patients who reported severe adverse events was similar with zolmitriptan 2.5 mg (4%) and placebo (5%). The most frequently reported adverse events with zolmitriptan in the placebo-controlled clinical studies were asthenia, heaviness (other than chest or neck), dry mouth, nausea, dizziness, somnolence, paresthesia and warm sensations. The type and severity of the adverse events was not influenced by gender (although the frequency of reported adverse events was higher in females, as was the case in the placebo group), age, presence of aura prior to the attack, association of migraine with menstruation, concurrent medication, or by the addition of a second zolmitriptan dose. Zolmitriptan showed a similar tolerability profile in the long-term study, in which a low withdrawal rate due to adverse events of 8% was observed. Zolmitriptan was not associated with an increased frequency of central nervous system-related adverse events in a comparative study of sumatriptan, despite pre-clinical and neurophysiological evidence of a dual peripheral and central action of zolmitriptan. Moreover, zolmitriptan doses of 5-20 mg produced no statistically significant effects on objective assessments of psychometric function. Zolmitriptan had no clinically significant effects on blood pressure (even in patients with controlled mild to moderate hypertension or impaired renal function), ECGs (e.g. there was no evidence of ischemic events) or clinical chemistry, hematological or urinalysis measurements. In summary, zolmitriptan is well tolerated, particularly at the recommended dose of 2.5 mg. Zolmitriptan has a well-defined dose-response with 2.5 mg proving highly effective and optimizing the benefit/risk ratio of treatment. Thus, zolmitriptan is well suited as an acute oral treatment for migraine in the outpatient setting.
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PMID:Tolerability profile of zolmitriptan (Zomig; 311C90), a novel dual central and peripherally acting 5HT1B/1D agonist. International clinical experience based on > 3000 subjects treated with zolmitriptan. 939 16

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of almotriptan are reviewed. Migraine is a common disorder with a serious impact on quality of life. Newer serotonin-receptor agonists have been developed with the aim of improving pharmacokinetic characteristics. Almotriptan, a selective agonist of serotonin receptors 1B and 1D, carries FDA-approved labeling for use in the management of migraine with or without aura in adults. The efficacy and receptor affinity resemble those of sumatriptan, but almotriptan has a more favorable pharmacokinetic profile. It has a rapid onset of action, an oral bioavailability of 70-80%, and a longer half-life than sumatriptan. In clinical trials, almotriptan has been significantly more effective than placebo and as effective as sumatriptan. However, it has been associated with better tolerability and greater patient satisfaction. In clinical trials, the most commonly reported adverse effects were nausea, dry mouth, dizziness, somnolence, fatigue, vomiting, and paresthesia. Almotriptan is contraindicated in patients with known ischemic heart disease, coronary vasospasm, and other significant cardiovascular disorders. Almotriptan has a lower acquisition cost than other triptans and possibly lower overall health care costs because of a lower frequency of cardiovascular adverse effects. The recommended dose of almotriptan is one 6.25- or 12.5-mg tablet given at the onset of symptoms. Almotriptan is effective for the management of migraine and offers the potential for fewer adverse effects than other agents in its class.
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PMID:Efficacy and safety of almotriptan malate for migraine. 1245 2

Frovatriptan succinate is one of the most recent serotonin receptor agonists to receive FDA, approved labelling for use in the acute management of migraine with or without aura in adults. The mechanism of action of frovatriptan is thought to be similar to that of a serotonin agonist. However, frovatriptan has distinctive pharmacokinetic and pharmacologic properties, chiefly, a high affinity for serotonin receptors 1B and 1D and a long elimination half-life; frovatriptan was shown to be more selective for cerebral than coronary arteries, a property which makes frovatriptan more favourable in patients at risk of coronary artery disease. Additionally, frovatriptan has a half-life of approximately 25 h, substantially longer than that of any other agent within its class. This property makes frovatriptan suitable for patients who typically suffer migraines of long duration and/or those who suffer migraine recurrence. The efficacy of frovatriptan in the treatment of acute migraine was demonstrated in five double-blind, randomised, placebo-controlled trials. At 2h, headache response rates for frovatriptan 2.5 mg ranged from 38 to 40% compared to 22-35% for placebo. Headache recurrence for frovatriptan 2.5 mg at 24h ranged from 9 to 14% compared with 18% in placebo subjects. Frovatriptan has no clinically significant pharmacokinetic interactions with drugs used for migraine prophylaxis or with commonly prescribed medications. Adverse effects of frovatriptan including dizziness, paresthesia, dry mouth, fatigue and flushing were generally mild and well tolerated. Given the fact that patient response to serotonin agonists is individualised, and selecting an effective agent may involve trial and error, frovatriptan is a welcome alternative in the acute management of migraine.
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PMID:Frovatriptan succinate, a 5-HT1B/1D receptor agonist for migraine. 1531 27

Frovatriptan is an orally active 5-hydroxytryptamine (5-HT) receptor agonist which binds with high affinity to 5-HT(1B) and 5-HT(1D) receptors. Earlier clinical trials demonstrated that frovatriptan 2.5 mg is significantly more effective than placebo in the acute management of migraine and its associated symptoms. More recently, frovatriptan was shown to be effective in the management of menstrual migraine. The incidence of menstrual migraine in subjects receiving frovatriptan 2.5 mg twice daily during the six day perimenstrual period was 41% compared with 67% with placebo. Frovatriptan treatment is generally well tolerated. The most commonly reported adverse effects were dizziness, paresthesia, dry mouth, and fatigue. Pharmacologic studies demonstrated that frovatriptan is cerebroselective. Its selectivity for cerebral vessels lessens the potential for undesirable peripheral effects. Frovatriptan has a terminal deposition half-life of approximately 26 hours, which appears to be independent of age, gender, and renal function. This imparts that frovatriptan may be particularly well suited to patients with prolonged migraines and those who suffer migraine recurrence. Frovatriptan does not alter cytochrome P450 (CYP450) isoenzymes, as such it is unlikely to affect the metabolism of other drugs. No dosage adjustments are necessary based on age, renal, or mild to moderate hepatic impairment. Apart from its efficacy in the acute management of migraine, frovatriptan is an effective agent when used as either acute therapy or as intermittent prophylaxis therapy of menstrual migraines, particularly in women who do not respond to conventional therapies.
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PMID:Frovatriptan: a review of pharmacology, pharmacokinetics and clinical potential in the treatment of menstrual migraine. 1836 Jun 5

The initiation of a prophylactic treatment for migraine depends on the frequency of migraine attacks and the extent of the function disability associated with these attacks. Antidepressants have good evidence of efficacy in the prophylactic treatment for migraine. In general, among the antidepressants, amitriptyline is the most frequently prescribed by headache specialists. Several clinical trials on this drug have also evidenced the remarkable benefits of amitriptyline in the prophylactic treatment of migraine attack. In evidence-based guidelines developed by Japanese Headache Society and American Neurological Association, it is classified as a Group 1 drugs (effective drug for the prevention of migraine attack). Moreover, these drugs are more useful in cases where there is comorbidity with conditions such as depression. The side-effects of these drugs are sleepiness and dry mouth. Administration of amytriptyline at low dose can reduce the frequency of side effects such as sleepiness.
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PMID:[Antidepressants in migraine prophylaxis]. 1988 39

Flupirtine is a centrally acting, non-opioid analgesic that is available in a number of European countries for the treatment of a variety of pain states. The therapeutic benefits seen with flupirtine relate to its unique pharmacological properties. Flupirtine displays indirect NDMA receptor antagonism via activation of potassium channels and is the first representative of a pharmacological class denoted the 'selective neuronal potassium channel openers'. The generation of the M-current is facilitated by flupirtine via the opening of neuronal Kv7 potassium channels. The opening of these channels inhibits exaggerated neuronal action potential generation and controls neuronal excitability. Neuronal hyperexcitability is a physiological component of many pain states such as chronic pain, migraine and neurogenic pain. Although large-scale clinical trials are lacking, the clinical trial database available to date from smaller-scale studies, together with extensive clinical experience, indicate that flupirtine effectively reduces chronic musculoskeletal pain, migraine and neuralgias, amongst other types of pain. In addition, flupirtine produces, at recommended clinical doses, muscle-relaxing effects in the presence of abnormally increased muscle tension. Its analgesic and muscle-relaxant properties were comparable to tramadol and chlormezanone, respectively, in two prospective trials in patients with lower back pain. Cytoprotective, anti-apoptotic and antioxidant properties have also been associated with flupirtine use in a small number of studies to date. When provided as combination therapy with morphine, flupirtine increases the antinociceptive activity of morphine 4-fold. Flupirtine displays superior tolerability when compared with tramadol and pentazocine. The most common adverse effects associated with flupirtine use are drowsiness, dizziness, heartburn, dry mouth, fatigue and nausea. With respect to its molecular structure, mechanism of action and adverse event profile, flupirtine is a unique drug. Flupirtine is an analgesic with many potential therapeutic benefits that may prove useful in the treatment of many disease states.
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PMID:Flupirtine in pain management: pharmacological properties and clinical use. 2083 97


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