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)

Preclinical studies indicate that dihydropyridine-type calcium channel antagonists modulate dopamine neurotransmitter function and can reduce cocaine-reinforced behaviors. Amlodipine, a long-acting dihydropyridine-type calcium channel antagonist related to isradipine and nifedipine, was administered in open label fashion for 12 weeks to 26 cocaine-dependent patients. In subjects expressing cocaine craving, craving significantly declined during the course of the 12 weeks. Five individuals reported flushing, headache, fatigue, nocturia, nausea, and lightheadedness. No conclusions regarding efficacy can be made due to the small number of subjects and the open-label design.
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PMID:Amlodipine treatment of cocaine dependence. 1043 93

Migraine has become an important topic in the field of complex genetic disorders. The identification of a gene on chromosome 19p encoding for an alpha 1A calcium channel subunit causing familial hemiplegic migraine has led to the classification of migraine as a channelopathy. More recently, efforts have been made to clarify the genetics of other primary headaches.
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PMID:Genetics of primary headaches. 1049 69

Following the recent discovery of neural calcium channel mutations in familial hemiplegic migraine, genetic linkage and association studies have been performed world-wide in an effort to unveil the genetic basis of the more common types of migraine too. Mutations in neural calcium channels, mitochondrial DNA, serotonin receptors and transporter, dopamine receptors and genetic prothrombotic risk factors have been especially investigated and are discussed here. No unambiguous conclusions have, however, been reached. FHM remains an isolated success story in the quest for the genetic basis of migraine.
Cephalalgia 2000 Feb
PMID:Molecular genetics of migraine headaches: a review. 1081 41

Angiotensin II receptor blockers (ARBs) represent a new class of effective and well tolerated orally active antihypertensive agents. Recent clinical trials have shown the added benefits of ARBs in hypertensive patients (reduction in left ventricular hypertrophy, improvement in diastolic function, decrease in ventricular arrhythmias, reduction in microalbuminuria, and improvement in renal function), and cardioprotective effect in patients with heart failure. Several large long-term studies are in progress to assess the beneficial effects of ARBs on cardiac hypertrophy, renal function, and cardiovascular and cerebrovascular morbidity and mortality in hypertensive patients with or without diabetes mellitus, and the value of these drugs in patients with heart disease and diabetic nephropathy. The ARBs specifically block the interaction of angiotensin II at the AT1 receptor, thereby relaxing smooth muscle, increasing salt and water excretion, reducing plasma volume, and decreasing cellular hypertrophy. These agents exert their blood pressure-lowering effect mainly by reducing peripheral vascular resistance usually without a rise in heart rate. Most of the commercially available ARBs control blood pressure for 24 h after once daily dosing. Sustained efficacy of blood pressure control, without any evidence of tachyphylaxis, has been demonstrated after long-term administration (3 years) of some of the ARBs. The efficacy of ARBs is similar to that of thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors or calcium channel blockers in patients with similar degree of hypertension. Higher daily doses, dietary salt restriction, and concomitant diuretic or ACE inhibitor administration amplify the antihypertensive effect of ARBs. The ARBs have a low incidence of adverse effects (headache, upper respiratory infection, back pain, muscle cramps, fatigue and dizziness), even in the elderly patients. After the approval of losartan, five other ARBs (candesartan cilexetil, eprosartan, irbesartan, telmisartan, and valsartan) and three combinations with hydrochlorothiazide (irbesartan, losartan and valsartan) have been approved as antihypertensive agents, and some 28 compounds are in various stages of development. The ARBs are non-peptide compounds with varied structures; some (candesartan, losartan, irbesartan, and valsartan) have a common tetrazolo-biphenyl structure. Except for irbesartan, all active ARBs have a carboxylic acid group. Candesartan cilexetil is a prodrug, while losartan has a metabolite (EXP3174) which is more active than the parent drug. No other metabolites of ARBs contribute significantly to the antihypertensive effect. The variation in the molecular structure of the ARBs results in differences in the binding affinity to the receptor and pharmacokinetic profiles. The differences observed in lipid solubility, absorption/distribution, plasma protein binding, bioavailability, biotransformation, plasma half-life, and systemic elimination influence the time of onset, duration of action, and efficacy of the ARBs. On the basis of the daily mg dose, the antihypertensive potency of the ARBs follows the sequence: candesartan cilexetil > telmisartan approximately = losartan > irbesartan approximately = valsartan > eprosartan. After oral administration, the ARBs are rapidly absorbed (time for peak plasma levels = 0.5-4 h) but they have a wide range of bioavailability (from a low of 13% for eprosartan to a high of 60-80% for irbesartan); food does not influence the bioavailability, except for valsartan (a reduction of 40-50%) and eprosartan (increase). A limited dose-peak plasma levels/areas under the plasma level-time curve proportionality is observed for some of the ARBs. Most of these drugs have high plasma protein binding (95-100%); irbesartan has the lowest binding among the group (90%). The steady-state volumes of distribution vary from a low of 9 L (candesartan) to a high of 500 L (telmisartan). (ABSTRACT TRUNCATE
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PMID:Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension. 1085 85

The objective of this study was to investigate the safety and efficacy of intranasal civamide for the acute treatment of migraine headache with or without aura. Civamide is a vanilloid receptor agonist and neuronal calcium channel blocker that inhibits the neuronal release of excitatory neurotransmitters (e.g. calcitonin gene-related peptide (CGRP) and substance P (SP)) and depletes the neurones of the trigeminal plexus of their neurotransmitter content. Applied intranasally, the release of neurotransmitters to meningeal and dural blood vessels should be decreased, along with the resultant vasodilatation, plasma extravasation, and histamine/serotonin release. Subsequent migraine headache pain may also be diminished. Thirty-four patients were enrolled into a double-blind study of intranasal civamide, and randomized to receive a single dose of either 20 microg or 150 microg of civamide, for the treatment of a single migraine headache, with or without aura, of moderate to severe pain. At 2 h post-dose, 55.6% of patients treated with either dose had a decrease in pain severity, with 22.2% of patients being pain-free. At 4 h post-dose, 72.7% of patients treated with either dose had a decrease in pain severity, with 33.0% of patients being pain-free. Adverse events were similar for both dosages, with 91.2% of patients experiencing nasal burning and 44.1% of patients experiencing lacrimation. No systemic side-effects were observed. Based upon the results of this study, intranasal civamide may be effective in the acute treatment of migraine headache. Given civamide's proposed mechanism of action, intranasal civamide should be substantially more effective for prophylaxis than acute treatment of migraine. A study evaluating its efficacy in prophylaxis of migraine is currently planned.
Cephalalgia 2000 Jul
PMID:Intranasal civamide for the acute treatment of migraine headache. 1107 45

Migraine is a debilitating neurological disorder characterized by recurrent attacks of severe headache. The disorder is highly prevalent, affecting approximately 12% of Caucasian populations. It is well known that migraine has a strong genetic component, although the type and number of genes involved is not yet clear. However, the calcium channel gene, CACNA1A, on chromosome 19 contains mutations responsible for familial hemiplegic migraine, a rare and severe subtype of migraine. There is also evidence to suggest that serotonin- and dopamine-related genes may be involved in the pathogenesis of migraine. This study employed a linkage and association approach to investigate neurotransmitter-related migraine candidate genes. Polymorphisms within the dopamine beta-hydroxylase (DBH) gene, serotonin transporter gene (SERT), and dopamine receptor gene (DRD2) were tested in 177 unrelated Caucasian migraineurs and 182 control individuals. In addition, an independent sample of 82 families affected with migraine was examined. Unrelated case-control association analysis of a DBH intragenic dinucleotide polymorphism indicated altered allelic distribution between migraine and control groups (chi2 = 16.53, P=0.019). Furthermore, the transmission/disequilibrium test, which was implemented on the family data, also indicated distortion of allele transmission for the same DBH marker (chi2 = 4.44, P=0.035). Together, these results provide evidence for allelic association of the DBH gene with typical migraine susceptibility (Fisher's combined P value =0.006) and indicate that further research into the role of the DBH gene in the etiology of migraine is warranted.
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PMID:Evidence for allelic association of the dopamine beta-hydroxylase gene (DBH) with susceptibility to typical migraine. 1108 95

Spreading depressions (SD) occur in association with ischaemia, epilepsy and migraine. Intracellular calcium oscillations have been suggested to be involved in the generation and propagation of SD. The present study was performed to study the mechanism of conditioning guinea pig hippocampal slices by the T-type calcium channel blockers NiCl2 and amiloride. SD-like fluctuations of DC potential were recorded by inserting microelectrodes into the CA1 and CA3 regions. The SD occurrence was significantly greater with 10 micromol/l NiCl2 as well as with 25 and 50 micromol/l amiloride than with other concentrations of these substances. The concentration response curve was inversely U-shaped with the maximum repetition rates of SDs being achieved at 10 micromol/l NiCl2 as well as at 25 and 50 micromol/l amiloride. SD occurrence could be completely blocked by the NMDA antagonist APV (10 micromol/l) in all cases. These data demonstrate that modulation of the Ca2+ dynamics conditioned guinea pig hippocampal slices and increased their susceptibility to generate SD.
Cephalalgia 2000 Oct
PMID:NiCl2 and amiloride induce spreading depression in guinea pig hippocampal slices. 1116 5

The treatment of migraine headache in children depends on the following: a) defining the underlying cause; b) the frequency of the attacks; and c) the severity of the disability produced by the pain. Any medication taken to relieve pain is most effective if taken at maximum dose at the onset of the headache. The dose should be the maximum recommended by weight or age. Triptans are also more effective if used early. Over-the-counter (OTC) analgesics are often effective in relieving pediatric headache and should be tried before prescription drug therapy is attempted. The more frequent a child's headaches are, the greater the danger that repeated doses of pain medications, including those purchased OTC, will lead to a chronic headache syndrome as the medication is reduced. Recurrent severe headaches, occurring more than once a week and resulting in interruption of normal activities or poor concentration, need to be treated with prophylactic medications taken daily so that the number of headaches can be reduced. Amitriptyline, propanolol, and periactin are the most frequently used drugs to block headaches, but valproate, verapamil, or other calcium channel blockers and other antidepressants are also useful. Biofeedback, relaxation, or cognitive therapies can also reduce headache frequency in children with both migraine and tension headaches. Headaches that are intractable to oral medication for the acute relief of pain may respond more rapidly to an efficiently absorbed drug administered by nasal spray or subcutaneously. The initial dose of an injectable drug should be given in a situation where a physician is immediately available. Recurrent headaches that have occurred over more than 6 months and that are associated with a normal neurologic examination are almost never caused by an intracranial lesion. Routine CT and MRI scans or an electroencephalogram (EEG) are generally unnecessary for these patients because these scans are rarely of value in these patients unless there is a history of another neurologic disorder or the headaches are focal, relentless, and worsening over time.
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PMID:Childhood Migraine Headache Syndromes. 1128 41

The paper presents the results of experimental studies and clinical trials associated with mechanism underlying nervous system damage and pharmacological interventions to be employed in such processes. Abnormal lipid peroxidation was demonstrated in experimental seizures, epilepsy and cerebral stroke. The authors presented the mechanism of calcium channel blockers activity in epilepsy and their experience in employing such agents in epileptic patients. Results of studies on S-100 protein determinations as a marker of the blood-brain barrier damage in epilepsy and hydrocephalus were discussed, along with the employment of evoked potentials in diagnostic management of headaches and the effects of complex treatment of epilepsy in children using Nootropil. Selected data on experimental valproate encephalopathy were also presented. The authors believe that these studies contribute to the understanding of mechanism that are responsible for nervous system dysfunction, as well as to the evaluation and treatment of their effects.
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PMID:[Studies of damaged processes in the nervous system and possibilities of neuroprotection]. 1135 9

Sublingual (SL) apomorphine (2 to 6 mg) has been shown to be effective for treatment of male erectile dysfunction. Many patients with erectile dysfunction are also being treated for systemic hypertension and/or cardiovascular disease. In a double-blind, randomized, placebo-controlled, crossover trial, SL apomorphine 5 mg and placebo were administered on alternate days to 162 men who were on long-term therapy (> or =4 weeks) with angiotensin-converting enzyme inhibitors, beta blockers, diuretics, calcium channel blockers, alpha(1) blockers, or short- or long-acting nitrates. Blood pressure and heart rate were measured before and after dosing; cardiac rhythm was recorded by 4-hour Holter monitoring. The only potentially clinically significant interactions between SL apomorphine and the antihypertensive agents or short-acting nitrates were greater orthostatic decreases in systolic blood pressure in the alpha-blocker and calcium channel blocker groups (-10 and -6 mm Hg vs placebo, respectively). Administration of SL apomorphine after dosing with long-acting nitrates resulted in significant decreases in blood pressure when patients were standing (mean systolic change, -5 to -9 mm Hg 30 to 60 minutes postdose, p <0.05; mean diastolic change, -3 to -4 mm Hg 50 to 60 minutes postdose, p <0.05). The most common adverse events with SL apomorphine were dizziness, nausea, and headache. Syncope occurred in 1 patient in the beta-blocker group; symptomatic hypotension occurred in 2 patients each in the short- and long-acting nitrate groups. Thus, in patients receiving common antihypertensive agents and short-acting nitrates, as well as in most patients receiving long-acting nitrates, SL apomorphine at higher than recommended doses produced no clinically significant changes in heart rate or blood pressure greater than changes seen with SL apomorphine alone.
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PMID:Cardiovascular safety of sublingual apomorphine in patients on stable doses of oral antihypertensive agents and nitrates. 1158 43


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