Disease relevance of CI 945

• Treatment of ciguatera poisoning with gabapentin [1].
• Gabapentin for postherpetic neuralgia [2].
• Gabapentin for painful diabetic neuropathy [3].
• OBJECTIVE: To evaluate the effect of gabapentin monotherapy on pain associated with diabetic peripheral neuropathy [4].
• Somnolence, dizziness, ataxia, peripheral edema, and infection were all more frequent in the gabapentin group, but withdrawals were comparable in the 2 groups (15 [13.3%] in the gabapentin group vs 11 [9.5%] in the placebo group) [5].

Psychiatry related information on CI 945

• Gabapentin in the treatment of bipolar disorder [6].
• Gabapentin as a potential treatment for anxiety disorders [7].
• Gabapentin for behavioral dyscontrol with mental retardation [8].
• Treatment of idiopathic restless legs syndrome (RLS) with gabapentin [9].
• Clinical predictors of response to lamotrigine and gabapentin monotherapy in refractory affective disorders [10].

High impact information on CI 945

• Two-photon imaging of live exposed cortex showed that several antiepileptic agents, including valproate, gabapentin and phenytoin, reduced the ability of astrocytes to transmit Ca(2+) signaling [11].
• Alternatively, AEDs may specifically target pathological channels; for example, gabapentin is a ligand of alpha2delta voltage-activated calcium channel subunits that are overexpressed in sensory neurons after nerve injury [12].
• Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: a randomized controlled trial [4].
• By intent-to-treat analysis, subjects receiving gabapentin had a statistically significant reduction in average daily pain score from 6.3 to 4.2 points compared with a change from 6.5 to 6.0 points in subjects randomized to receive placebo (P<.001) [5].
• In an anecdotal report, complete resolution of chemotherapy-induced nausea was seen in a patient with breast cancer, after she was placed on the anticonvulsant gabapentin [13].

Chemical compound and disease context of CI 945

• Benefit of vitamin E, riluzole, and gabapentin in a transgenic model of familial amyotrophic lateral sclerosis [14].
• BACKGROUND: Reports of gabapentin use in diabetic peripheral neuropathy pain stimulate a need for controlled trials to determine its comparative efficacy to the therapeutic standard of amitriptyline hydrochloride [15].
• METHODS: Forty-five patients with treatment refractory bipolar (n = 35) or unipolar (n = 10) affective disorder participated in a clinical study evaluating six weeks of treatment with lamotrigine, gabapentin, or placebo monotherapy given in a double-blind, randomized fashion with two subsequent cross-overs to the other agents [10].
• We recommend use of vigabatrin or gabapentin, but not felbamate, lamotrigine, or tiagabine, in patients with acute porphyria and seizures [16].
• This same response is seen after initiating treatment of sleep apnea with nasal continuous positive airway pressure (CPAP), and can also occur in patients with other sleep disorders in response to particular medications, such as valproate or gabapentin [17].

Biological context of CI 945

• Structural analysis shows that the bulky gabapentin is enclosed in the active-site cavity by the shift of a flexible loop that enlarges the active-site cavity [18].
• Oxcarbazepine has fewer drug interactions than carbamazepine, and gabapentin has one, a reduction of felbamate renal elimination [19].
• Clinical pharmacokinetics of gabapentin [20].
• Up to a concentration of 1 mM, gabapentin displayed no agonistic effects on either the GABA(B(1a,2)) or the GABA(B(1b,2)) heterodimer, when these were expressed in Xenopus laevis oocytes or mammalian cells and assayed by means of electrophysiology, calcium mobilization, inositol phosphate, and fluorometry assays [21].
• In fact, analysis of the combined data from the phase II and III trials revealed a significantly more rapid decline of forced vital capacity in patients treated with gabapentin [22].

Anatomical context of CI 945

• Here we report that gabapentin is an agonist at the GABA(B) gb1a-gb2 heterodimer coupled to Kir 3.1/3.2 inwardly rectifying K+ channels in Xenopus laevis oocytes [23].
• Gabapentin did not displace [(3)H]GABA from GABA(B) receptor sites in rat synaptic membranes [21].
• Because of high levels of GABA(B(1a)) in the canine nodose ganglion, this finding indirectly supports the inactivity of gabapentin on the GABA(B(1a,2)) heterodimer demonstrated in various in vitro assays [21].
• This case demonstrates the correspondence between rCBF and pain associated with spinal cord injury and also suggests the potential utility of gabapentin for treatment of this central pain state [24].
• Gabapentin (GP) has been shown to have antihyperalgesic properties and the site of drug action is reported to be the central nervous system [25].

Associations of CI 945 with other chemical compounds

• GABA was elevated in patients taking gabapentin compared with 14 complex partial epilepsy patients, matched for antiepileptic drug treatment [26].
• EVIDENCE ACQUISITION: A MEDLINE search was conducted, limiting searching to double-blind, randomized, controlled trials (1978 to present) of antiepileptic drugs (carbamazepine, gabapentin, pregabalin, topiramate, and lamotrigine) used in the treatment of chronic neuropathic pain [27].
• The NNT was 2.6 for tricyclic antidepressants, 6.7 for selective serotonin reuptake inhibitors, 2.5 for anticonvulsant sodium channel blockers, 4.1 for the anticonvulsant calcium channel blocker gabapentin, and 3.4 for the mixed opioid and monoaminergic drug tramadol, as calculated from a sufficiently large number of patients [28].
• This controlled comparative study evaluated the efficacy of lamotrigine (LTG) and gabapentin (GBP) monotherapy versus placebo (PLC) [29].
• Clinical pharmacokinetics of newer antiepileptic drugs. Lamotrigine, vigabatrin, gabapentin and oxcarbazepine [30].

Gene context of CI 945

• 4. NCX8001, but not gabapentin, counteracted in a concentration-dependent fashion lipopolysaccharide-induced overexpression and function of iNOS in RAW264.7 macrophages cell line [31].
• Gabapentin actions on N-methyl-D-aspartate receptor channels are protein kinase C-dependent [32].
• Gabapentin (1-50 mg/kg, intraperitoneally (i.p.)) was able to antagonize audiogenic seizures in Dilute Brown Agouti DBA2J (DBA/2) mice in a dose-dependent manner [33].
• A 13-year-old boy with bipolar I disorder, manic episode, and ADHD, was treated with gabapentin 1,500 mg/day as add-on therapy to carbamazepine and showed a marked response within 1 month [34].
• Gabapentin had no effect, whereas the combination of CNTF and BDNF enhanced survival to 177+/-9% [35].

Analytical, diagnostic and therapeutic context of CI 945

• INTERVENTION: A 4-week titration period to a maximum dosage of 3600 mg/d of gabapentin or matching placebo [5].
• Adverse events experienced significantly more frequently in the gabapentin group were dizziness (20 [24%] in the gabapentin group vs 4 [4.9%] in the control group; P<.001) and somnolence (19 [23%] in the gabapentin group vs 5 [6%] in the control group; P = .003) [4].
• Effect of gabapentin on nausea induced by chemotherapy in patients with breast cancer [13].
• CONCLUSION: Gabapentin is effective in improving analgesia in patients with neuropathic cancer pain already treated with opioids [36].
• Randomized double-blind study comparing the efficacy of gabapentin with amitriptyline on diabetic peripheral neuropathy pain [15].

References