Cellular and molecular action of the putative GABA-mimetic, gabapentin

Maneuf, Yannick P.; Gonzalez, Maria; Sutton, Katherine S.; Chung, Fung Lung; Pinnock, R.D.; Lee, K.

doi:10.1007/s00018-003-2108-x

Cited by 120 publications

(27 citation statements)

References 78 publications

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“…GBP, a member of a class of anticonvulsants, has a high-affinity binding site on the α2δ subunit of the voltage-gated Ca 2+ channel (VGCC) in the CNS [64–66] . GBP modulates neurotransmission presynaptically by inhibiting the release of various neurotransmitters from hyper-excitable or pathophysiological cells via blocking the trafficking of the α2δ1 subunit to the presynaptic membrane [67–70] .…”

Section: Discussionmentioning

confidence: 99%

“…So far, it is not clear where and how GBP acts to produce anti-allodynic effects in this animal model of CPSP, since the systemic route of administration can result in anti-allodynic efficacy at both spinal and supraspinal sites [66,69] . Moreover, the molecular and cellular mechanisms underlying central post-stroke mechanical pain hypersensitivity remain unclear.…”

Section: Discussionmentioning

confidence: 99%

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Post-stroke pain hypersensitivity induced by experimental thalamic hemorrhage in rats is region-specific and demonstrates limited efficacy of gabapentin

Yang

Han

et al. 2014

Neurosci. Bull.

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Intractable central post-stroke pain (CPSP) is one of the most common sequelae of stroke, but has been inadequately studied to date. In this study, we first determined the relationship between the lesion site and changes in mechanical or thermal pain sensitivity in a rat CPSP model with experimental thalamic hemorrhage produced by unilateral intra-thalamic collagenase IV (ITC) injection. Then, we evaluated the efficacy of gabapentin (GBP), an anticonvulsant that binds the voltage-gated Ca2+ channel α2δ and a commonly used anti-neuropathic pain medication. Histological case-by-case analysis showed that only lesions confined to the medial lemniscus and the ventroposterior lateral/medial nuclei of the thalamus and/or the posterior thalamic nucleus resulted in bilateral mechanical pain hypersensitivity. All of the animals displaying CPSP also had impaired motor coordination, while control rats with intra-thalamic saline developed no central pain or motor deficits. GBP had a dose-related anti-allodynic effect after a single administration (1, 10, or 100 mg/kg) on day 7 post-ITC, with significant effects lasting at least 5 h for the higher doses. However, repeated treatment, once a day for two weeks, resulted in complete loss of effectiveness (drug tolerance) at 10 mg/kg, while effectiveness remained at 100 mg/kg, although the time period of efficacious analgesia was reduced. In addition, GBP did not change the basal pain sensitivity and the motor impairment caused by the ITC lesion, suggesting selective action of GBP on the somatosensory system.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Post-stroke pain hypersensitivity induced by experimental thalamic hemorrhage in rats is region-specific and demonstrates limited efficacy of gabapentin

Yang

Han

et al. 2014

Neurosci. Bull.

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“…Gabapentin works by reducing lesion-induced hyperexcitability of posterior horn neurons, which is responsible for central sensitization [1]. The mechanism of the antihyperalgesic action may be a result of the postsynaptic binding of gabapentin to the alpha 2 -delta subunit of the dorsal horn neurons' voltage-dependent calcium channels, causing decreased calcium entry into nerve endings and thus decreased release of neurotransmitters.…”

Section: Introductionmentioning

confidence: 99%

Gabapentin in Acute Postoperative Pain Management

Chang

Challa

Shah

et al. 2014

BioMed Research International

101

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Gabapentin (1-aminomethyl-cyclohexaneacetic acid) is an amino acid that has the structure of the neurotransmitter γ-aminobutyric acid (GABA). It is a novel drug used for the treatment of postoperative pain with antihyperalgesic properties and a unique mechanism of action. Gabapentin and the related, more potent compound pregabalin have been shown to be beneficial in the treatment of neuropathic pain as well as postoperative pain following spinal surgery and hysterectomy. This study reviews five aspects of gabapentin: (1) chemical and structural characteristics; (2) pharmacokinetics and pharmacodynamics; (3) application in acute pain management; (4) adverse effects; and (5) drug safety. Overall, gabapentin has been reported to be a safe and efficacious drug for the treatment of postoperative pain.

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“…Gabapentin has been shown in animal models to have anxiolytic-like effects and has been used as an analgesic [16]. Gabapentin has been reported to reduce craving [17,18] and other subjective effects of cocaine administration [19].…”

Section: Introductionmentioning

confidence: 99%

Double‐blind placebo‐controlled evaluation of the PROMETA™ protocol for methamphetamine dependence

et al. 2011

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Aims To evaluate the efficacy and safety of the PROMETA™ Protocol for treating methamphetamine dependence. Design A double-blind, placebo-controlled 108-day study with random assignment to one of two study conditions: active medication with flumazenil (2 mg infusions on days 1, 2, 3, 22, 23), gabapentin (1200 mg to day 40) and hydroxazine (50 mg to day 10) versus placebo medication (with active hydroxazine only). Setting Three substance abuse treatment clinics: two in-patient, one out-patient. Participants Treatment-seeking, methamphetamine-dependent adults (n = 120). Measurements Primary outcome was percentage of urine samples testing negative for methamphetamine during the trial. Findings No statistically significant between-group differences were detected in urine drug test results, craving, treatment retention or adverse events. Conclusions The PROMETA protocol, consisting of flumazenil, gabapentin and hydroxyzine, appears to be no more effective than placebo in reducing methamphetamine use, retaining patients in treatment or reducing methamphetamine craving.

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Cellular and molecular action of the putative GABA-mimetic, gabapentin

Cited by 120 publications

References 78 publications

Post-stroke pain hypersensitivity induced by experimental thalamic hemorrhage in rats is region-specific and demonstrates limited efficacy of gabapentin

Post-stroke pain hypersensitivity induced by experimental thalamic hemorrhage in rats is region-specific and demonstrates limited efficacy of gabapentin

Gabapentin in Acute Postoperative Pain Management

Double‐blind placebo‐controlled evaluation of the PROMETA™ protocol for methamphetamine dependence

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