Disease relevance of tiagabine

• Improvement of stiff-person syndrome with tiagabine [1].
• Possible drug-induced thrombocytopenia secondary to tiagabine [2].
• Based on these findings, we suggest that 1) tiagabine slows the development of hippocampal degeneration following ischemia, and 2) that mild, postischemic hypothermia is responsible, in large part, for the neuroprotective actions of this drug [3].
• Skin rash or psychosis occurred with similar frequencies among tiagabine- and placebo-treated patients [4].
• Adverse events associated with tiagabine are primarily CNS-related and include dizziness, asthenia, nonspecific nervousness and tremor [4].

Psychiatry related information on tiagabine

• Tiagabine and the treatment of refractory bipolar disorder [5].
• Tiagabine for posttraumatic stress disorder: a case series of 7 women [6].
• Tiagabine may be a therapeutic option for the treatment of anxiety disorders [7].
• Significant increases in Stage 3+4 sleep (i.e., slow-wave sleep) were found for tiagabine 4, 6, and 8 mg versus placebo, with a corresponding significant decrease in Stage 1 sleep (P < .05) [8].
• METHODS: Elderly subjects (aged 65-85 years) meeting DSM-IV-TR criteria for primary insomnia were randomly assigned to receive tiagabine 2, 4, 6, or 8 mg or placebo on 2 consecutive nights [8].

High impact information on tiagabine

• Disulfiram has been shown to reduce cocaine use in several clinical trials, while baclofen, modafinil, naltrexone, ondansetron, tiagabine, and topiramate have shown preliminary efficacy in initial clinical studies [9].
• Visual field constriction: accumulation of vigabatrin but not tiagabine in the retina [10].
• Other trials are needed to evaluate the use of topiramate and tiagabine in older patients with epilepsy [11].
• We report an open-label study of 25 children with complex partial seizures that assessed the pharmacokinetics and safety of a single dose of approximately 0.1 mg/kg tiagabine [12].
• The efficacy and tolerability of tiagabine in adult patients with post-traumatic stress disorder [13].

Chemical compound and disease context of tiagabine

• The selective GABA reuptake inhibitor tiagabine for the treatment of generalized anxiety disorder: results of a placebo-controlled study [14].
• This 10-week, randomized, open-label trial evaluated tiagabine in patients with generalized anxiety disorder (GAD), with paroxetine serving as a positive control [7].
• All drugs reduced the generalized seizures in amygdala kindled rats, but tiagabine and gabapentin furthermore attenuated afterdischarge duration of amygdala kindled seizures [15].
• Total percentage body weight changes during add-on therapy with tiagabine, carbamazepine and phenytoin [16].
• The ED50 value against clonic seizures (in mumol kg-1 at the time of maximal anticonvulsant effect) for tiagabine was 23 (0.5 h), and for NNC-711 was 72 (1 h), and for carbamazepine was 98 (2 h) [17].

Biological context of tiagabine

• Tiagabine decreased body temperature a maximum of 2.7 degrees C beginning 30 min into reperfusion and lasting 90 min [3].
• Newer anticonvulsants (i.e., gabapentin, tiagabine) with fewer drug interactions may be better alternatives when compared to older anticonvulsant agents [18].
• At 20 mg. kg.-1 tiagabine intravenously increased post-void residual volume a mean of 300% +/- 120% and decreased bladder capacity a mean of 14% +/- 3% [19].
• Pharmacodynamic analysis of the interaction between tiagabine and midazolam with an allosteric model that incorporates signal transduction [20].
• 2. Compared with vehicle, tiagabine had minimal effects on the temporal pattern of non-rapid eye movement sleep (non-REMS) and on the total time spent therein [21].

Anatomical context of tiagabine

• We used in vivo microdialysis to determine a suitable dosing regimen for tiagabine (NNC328) to elevate extracellular levels of GABA within the hippocampus [3].
• When normothermia was maintained both during and after ischemia in a separate group of tiagabine-treated animals, approximately 77% of the CA1 pyramidal cell layer was necrotic at 4 days [3].
• In the present study the effects of systemically administered tiagabine [30 mg/kg, ip (ED50)] were examined on audiogenic seizure (AGS) severity and neuronal firing in the inferior colliculus (IC) in the freely moving genetically epilepsy-prone rat (GEPR-9) [22].
• The present study examines the effect of tiagabine (a selective inhibitor of GABA transporter 1, GAT-1), SNAP-5114 (a semi-selective inhibitor of rat GAT-3/mouse GAT4) and NNC 05-2045 (a non-selective GABA uptake inhibitor) in modulating GABA levels in the hippocampus and thalamus [23].
• Whereas nipecotic acid and beta-alanine suppressed all forms of epileptiform activity albeit at high concentrations (1-5 mM), tiagabine was much more potent in blocking the hippocampal recurrent short discharges and the seizure-like events in the medial entorhinal cortex, but could not block the late recurrent discharges [24].

Associations of tiagabine with other chemical compounds

• The clinical pharmacokinetics of the newer antiepileptic drugs. Focus on topiramate, zonisamide and tiagabine [25].
• In addition, tiagabine significantly reduced the ischemic-induced elevation of glutamate levels in area CA1 during the postischemic period when GABA levels were elevated [3].
• We have shown that known GABA uptake inhibitors such as SK&F 89976-A, CI-966, and Tiagabine exhibit high affinity and selectivity for GAT-1 [26].
• The incidence of SUDEP with gabapentin, tiagabine, and lamotrigine clinical development programmes is in the range found in other populations with refractory epilepsy [27].
• This study was conducted to investigate the effects on the pharmacokinetics of tiagabine at steady state when coadministered with therapeutic doses of erythromycin [28].

Gene context of tiagabine

• To determine the involvement of the globus pallidus in mediating epilepsy, the effects of microinjection of a GABA uptake blocker (tiagabine), a benzodiazepine agonist (zolpidem) and a GABA-B receptor agonist (baclofen) on pentylenetetrazol (PTZ)-induced tonic seizure were examined in adult rats [29].
• Importantly, the increased extrasynaptic inhibition, even when facilitated in the presence of tiagabine, was not able fully to counteract enhanced seizure induction by GABAA antagonists [30].
• N-Methyl-exo-THPO was the most potent anticonvulsant among the exo-THPO compounds tested and only slightly less potent than tiagabine [31].
• Tiagabine exhibits dose-independent absorption, 90-95% bioavailability, high protein binding (96%), metabolism via hepatic cytochrome P450 enzymes (CYP3A subfamily), and displays first-order elimination pharmacokinetics [32].
• Cognitive and quality of life effects of differing dosages of tiagabine in epilepsy [33].

Analytical, diagnostic and therapeutic context of tiagabine

• One hundred sixty-two patients provided cognitive and quality of life data for the analyses and received the following treatments: placebo (n = 57), 16 mg/d tiagabine (n = 34), 32 mg/d tiagabine (n = 45), or 56 mg/d tiagabine (n = 26) at a fixed-dose for 12 weeks after a 4-week dose titration period [33].
• Exploratory regressions on these data in children and previous data in adults showed fairly strong relationships between body size and tiagabine clearance and volume of distribution, with body size explaining about 40 to 50% of the variability [12].
• Tiagabine significantly increased sleep efficiency, tendentially decreased wakefulness and prominently increased both SWS and low-frequency activity in the EEG within non-REM sleep [34].
• This 12-week, multicenter, double-blind study randomized patients to receive either tiagabine or placebo [13].
• MEASUREMENTS AND RESULTS: Polysomnography documented a SWS-enhancing effect of tiagabine [35].

References