Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gabapentin (GBP) is a antiepileptic drug (AED) indicated as adjunct therapy for treatment of partial seizures, with and without secondary generalization, in patients 12 and older with epilepsy. GBP (1-(aminomethyl) cyclohexaneacetic acid) is structurally related to gamma-aminobutyric acid (GABA), which readily crosses the blood-brain barrier. Radiolabeled GBP binds throughout the central nervous system in anatomic areas important in treatment of seizures. Its precise mechanism of action is unknown. An open-label, dose-ranging study of doses up to 1,800 mg produced > or =50% seizure reductions [responder rate (RR)] in 29% of patients with partial seizures. Three double-blind, placebo-controlled, parallel add-on trials at doses of 300-1,800 mg have produced RR of up to 28%, with a placebo RR of 8-10%. An active controlled, parallel group comparison of 600 mg to 2,400 mg in monotherapy conversion design showed no significant difference among the 600 mg, 1,200 mg, and 2,400 mg groups compared to a placebo group. An inpatient, active-controlled comparison of 300 mg and 3,600 mg in a parallel-design monotherapy trial showed that time to exit from the study was significantly longer for the 3,600-mg group and the completion rate significantly higher (53% vs. 17%) for patients receiving 3,600 mg/day vs. 300 mg/day of GBP. Successful double-blind, placebo-controlled trials in refractory childhood partial seizures and benign childhood epilepsy with centrotemporal spikes have been recently concluded. Absence was not successfully treated in one small double-blind trial. Open-label reports emphasize adjustments of patients to higher doses than those indicated in the package labeling. An open-label trial of GBP therapy in patients with partial seizures (n = 2,216) produced progressively greater seizure freedom rates as patients were titrated from > or =900 mg daily to > or = 1,800 mg daily (15.1% vs. 33.4%), with a similar effect on RR (18.1% vs. 44.9%). An add-on, open-label study treating partial seizures (n = 141) reported an RR of 71%, with 46% seizure-free in the last 8 weeks of treatment and doses up to 2,400 mg daily. A comparison trial of three doses of GBP to 600 mg of carbamazepine showed similar retention rates for 1,800 mg of GBP and 600 mg of CBZ. Another study reported 48% of patients experiencing 50% reduction, nine of whom had doses greater than 2,400 mg. Treatment in children has reported a 34.4% RR in 32 children with refractory partial seizures. A French open-label adjunctive trial documented a 33.9% RR; 13.4% were seizure-free during the evaluation period. Adverse experiences most commonly noted included somnolence, dizziness, and ataxia. Weight gain was sometimes reported with higher doses of GBP, and pediatric reports cite prominent behavioral changes, including hyperactivity, irritability, and agitation. GBP appears best used at doses at and potentially above those suggested in its package labeling. Although efficacy occurs at lower levels, increased GBP doses are associated with additional efficacy. Reports suggest that initiation at 2,400 mg or 3,600 mg may not be associated with increased adverse experiences. Titration to 900 or 1,200 mg on the first day of GBP therapy appear to be well tolerated.
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PMID:Gabapentin. 1053 Jun 96

Pregabalin (S-[+]-3-isobutylgaba) was designed as a lipophilic GABA (gamma-aminobutyric acid) analogue substituted at the 3'-position in order to facilitate diffusion across the blood-brain barrier. It was originally developed as an anticonvulsant agent, however it has been shown to be effective in the treatment of several disorders including hyperalgesia and behavioural disorders. Although its exact mode of action remains unclear, pregabalin interacts with the same binding site and has a similar pharmacological profile as its predecessor, gabapentin (1-[aminomethyl] cyclohexane acetic acid). Its main site of action appears to be on the alpha(2)delta subunit of voltage-dependent calcium channels, widely distributed throughout the peripheral and central nervous system. Pregabalin appears to produce an inhibitory modulation of neuronal excitability. In healthy volunteers, it is rapidly absorbed with peak blood concentrations within 1 h and it has a bioavailability of approximately 90%. In preclinical trials of anticonvulsant activity, pregabalin is three to ten times more potent than gabapentin. It is well-tolerated and associated with dose-dependent adverse effects (ataxia, dizziness, headache and somnolence) that are mild-to-moderate and usually transient. There are no known pharmacokinetic drug-drug interactions reported to date. Preliminary animal and human studies showed beneficial effects in both ethological and conflict models of anxiety, as well as having some sleep-modulating properties. In Phase II and III trials, pregabalin shows promising anxiolytic action when compared to placebo in generalised anxiety disorder, social phobia and panic disorder.
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PMID:Pregabalin: a new anxiolytic. 1266 21

Pregabalin, the pharmacologically active S-enantiomer of 3-aminomethyl-5-methyl-hexanoic acid, has a similar pharmacological profile to that of its developmental predecessor gabapentin, but showed greater analgesic activity in rodent models of neuropathic pain. The exact mechanism of action of pregabalin is unclear, although it may reduce excitatory neurotransmitter release by binding to the alpha2-delta protein subunit of voltage-gated calcium channels. Oral pregabalin at fixed dosages of 300 and 600 mg/day, administered three times daily, was superior to placebo in relieving pain and improving pain-related sleep interference in three randomised, double-blind, multicentre studies of 5-8 weeks' duration in a total of 724 evaluable patients with painful diabetic peripheral neuropathy (DPN). Significant reductions in weekly mean pain scores (primary endpoint) and sleep interference scores were observed at 1 week and sustained thereafter. A significant reduction in pain was apparent on the first day of treatment with pregabalin 300 mg/day. Twice daily fixed (600 mg/day) or flexible (150-600 mg/day) pregabalin was also effective in reducing pain and sleep interference in two 12-week placebo-controlled trials in a total of 733 randomised DPN patients. Pregabalin was well tolerated in DPN patients; mild-to-moderate dizziness, somnolence and peripheral oedema were the most common adverse events.
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PMID:Pregabalin: in the treatment of painful diabetic peripheral neuropathy. 1556 50

Pregabalin, the pharmacologically active S-enantiomer of 3-aminomethyl-5-methyl-hexanoic acid, has a similar pharmacological profile to that of its developmental predecessor gabapentin, but showed greater analgesic activity in rodent models of neuropathic pain. The exact mechanism of action of pregabalin is unclear, although it may reduce excitatory neurotransmitter release by binding to the alpha2-delta protein subunit of voltage-gated calcium channels. Oral pregabalin 150-600 mg/day, administered twice or three times daily, was superior to placebo in relieving pain and improving pain-related sleep interference in three randomised, double-blind, placebo-controlled, multicentre studies of 8-13 weeks' duration in a total of 776 evaluable patients with postherpetic neuralgia (PHN). Weekly mean pain scores (primary endpoint; assessed in all three studies) and weekly mean sleep interference scores (assessed in two studies) were significantly improved at 1 week. In two studies, significant improvements in daily mean pain scores were apparent on the first or second day of treatment with pregabalin administered three times daily. Pregabalin was generally well tolerated when force-titrated over 1 week to fixed dosages (maximum 600 mg/day) in clinical trials that enrolled most elderly PHN patients. Dizziness, somnolence and peripheral oedema of mild-to-moderate intensity were the most common adverse events.
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PMID:Pregabalin: in the treatment of postherpetic neuralgia. 1561 58

Pregabalin, the pharmacologically active S-enantiomer of 3-aminomethyl-5-methylhexanoic acid, possesses anticonvulsant activity. Pregabalin binds with high affinity and specificity to voltage-gated calcium channel alpha(2)-delta proteins. The putative mechanism of action of the drug is reduced excitatory neurotransmitter release caused by binding to the alpha(2)-delta protein, resulting in allosteric modulation of P/Q-type voltage-gated calcium channels. In three well designed trials, oral pregabalin as adjunctive therapy in patients with refractory partial seizures was significantly (p < or = 0.0007) more effective than placebo in reducing seizure frequency when administered at dosages of 150-600 mg/day (as two or three divided doses). Adjunctive pregabalin produced an overall mean 41.3% improvement from baseline in 28-day seizure-free rate in four long-term (maximum exposure 1764 days), open-label studies in 1480 patients. CNS-related effects (e.g. dizziness and somnolence) were the most frequent dose-related treatment-emergent adverse events associated with adjunctive pregabalin therapy.
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PMID:Pregabalin: as adjunctive treatment of partial seizures. 1574 Jan 80

Pregabalin, the pharmacologically active S-enantiomer of 3-aminomethyl-5-methyl-hexanoic acid, is a structural analogue of GABA, although it is not active at GABA receptors, nor does it acutely alter GABA uptake or degradation.black triangle Pregabalin binds with high affinity to the alpha2-delta subunit protein of voltage-gated calcium channels in CNS tissues and acts as a presynaptic modulator of the excessive release, in hyperexcited neurons, of various excitatory neurotransmitters. Binding of pregabalin to the alpha2-delta subunit appears necessary for its demonstrable anxiolytic, analgesic and anticonvulsant activities in animal models.black triangle Oral pregabalin, typically at dosages of 300-600 mg/day, was superior to placebo and similar to lorazepam 6 mg/day, alprazolam 1.5 mg/day and venlafaxine 75 mg/day in improving anxiety and depressive symptoms in patients with moderate-to-severe generalised anxiety disorder (GAD). Pregabalin had a rapid onset of anxiolytic activity relative to alprazolam and venlafaxine, which was evident after 1 week. Additionally, pregabalin (initial dosage 450 mg/day) was effective for the prevention of relapse of GAD over 34 weeks. Pregabalin was well tolerated during dosage escalation to fixed dosages (maximum 600 mg/day) over 7 days. Dizziness and somnolence, usually of mild to moderate severity, were the most common adverse events.black triangle The drug was not associated with a clinically significant medication withdrawal syndrome during a 1-week taper following 4 or 6 weeks' double-blind treatment.
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PMID:Pregabalin: in the treatment of generalised anxiety disorder. 1686 76