A summary of mechanistic hypotheses of gabapentin pharmacology

Taylor, Charles P.; Gee, N S; Su, Ti‐Zhi; Kocsis, Jeffery D.; Welty, Devin; Brown, Jason P.; Dooley, David; Boden, P.; Singh, Lakhbir

doi:10.1016/s0920-1211(97)00084-3

Cited by 724 publications

(409 citation statements)

References 90 publications

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“…8 Though the exact mechanism of action of gabapentin is not known, proposed mechanisms are its ability to: increase the concentration and the rate of synthesis of GABA in the brain; bind with high affinity to binding sites in brain tissues that are associated with an auxiliary subunit of voltage sensitive calcium channels (α 2 *subunits); reduce the release of monoamine neurotransmitters; inhibit voltage activated sodium channels; and increase serotonin concentrations in human blood. 9,10 Tramadol is a centrally acting opioid analgesic with an analgesic potency equivalent to pethidine. 11 It also modifies transmission of pain impulses by inhibition of monoamine re-uptake.…”

Section: Objectifmentioning

confidence: 99%

L’usage préventif de gabapentine diminue significativement la douleur postopératoire et les besoins d’analgésique de secours lors d’une cholécystectomie laparoscopique

Pandey

Priye

Singh

et al. 2004

Can J Anesth/J Can Anesth

192

150

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P Pu ur rp po os se e: : To evaluate the comparative preemptive effects of gabapentin and tramadol on postoperative pain and fentanyl requirement in laparoscopic cholecystectomy.M Me et th ho od ds s: : Four hundred fifty-nine ASA I and II patients were randomly assigned to receive 300 mg gabapentin, 100 mg tramadol or placebo in a double-blind manner two hours before laparoscopic cholecystectomy under general anesthesia. Postoperatively, patients' pain scores were recorded on a visual analogue scale every two hours for the initial 12 hr and thereafter every three hours for the next 12 hr. Patients received fentanyl 2 µg·kg -1 intravenously on demand. The total fentanyl consumption for each patient was recorded.R Re es su ul lt ts s: : Patients in the gabapentin group had significantly lower pain scores at all time intervals (2.65 ± 3.00, 1.99 ± 1.48, 1.40 ± 0.95, 0.65 ± 0.61) in comparison to tramadol (2.97 ± 2.35, 2.37 ± 1.45, 1.89 ± 1.16, 0.87 ± 0.50) and placebo (5.53 ± 2.22, 3.33 ± 1.37, 2.41 ± 1.19, 1.19 ± 0.56). Significantly less fentanyl was consumed in the gabapentin group (221.16 ± 52.39 µg) than in the tramadol (269.60 ± 44.17 µg) and placebo groups (355.86 ± 42.04 µg; P < 0.05). Sedation (33.98%), nausea/retching/vomiting (24.8%) were the commonest side effects in the gabapentin group whereas respiratory depression (3.9%) was the commonest in the tramadol group and vertigo (7.8%) in the placebo group. C Co on nc cl lu us si io on n: : Preemptive use of gabapentin significantly decreases postoperative pain and rescue analgesic requirement in laparoscopic cholecystectomy. (2,65 ± 3,00; 1,99 ± 1,48; 1,40 ± 0,95; 0,65 ± 0,61) que ceux du groupe tramadol (2,97 ± 2,35; 2,37 ± 1,45; 1,89 ± 1,16; 0,87 ± 0,50) ou placebo (5,53 ± 2,22; 3,33 ± 1,37; 2,41 ± 1,19; 1,19 ± 0,56). La demande de fentanyl a été significativement plus basse avec la gabapentine (221,16 ± 52,39 µg) qu'avec le tramadol (269,60 ± 44,17 µg) ou le placebo (355,86 ± 42,04 µg; P < 0,05). La sédation (33,98 %), les nausées/haut-lecoeur/vomissements (24,8 %) ERIPHERAL tissue injury provokes peripheral sensitization (a reduction in the threshold of nociceptor afferent peripheral terminals) and central sensitization (an activity dependent increase in the excitability of spinal neurons). 1,2 These changes contribute to the postinjury pain hypersensitivity state which manifests as an increase in the responsiveness to noxious stimuli and a decrease in the pain threshold, both at the site of injury and in the surrounding uninjured tissue. 1,2 The optimal form of treatment is that applied pre, intra and postoperatively to preempt the establishment of pain hypersensitivity during and after surgery. The preemptive treatment could be directed at the periphery, at inputs along sensory axons, and at central neurons. Different treatment regimens could be used at different times relative to surgery to maximize the prevention of pain in response to different levels of sensory inputs. 1,2 Gabapentin and tramadol both have demonstrated analgesic effect...

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Section: Objectifmentioning

confidence: 99%

L’usage préventif de gabapentine diminue significativement la douleur postopératoire et les besoins d’analgésique de secours lors d’une cholécystectomie laparoscopique

Pandey

Priye

Singh

et al. 2004

Can J Anesth/J Can Anesth

192

150

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“…This activitydependent mechanism would explain why vigabatrin prevents seizures with relatively little effect on normal cognition. A low incidence of cognitive side effects is a property shared with the anticonvulsant gabapentin, which shares the final common pathway of enhancement of nonvesicular GABA release (Kocsis and Honmou, 1994;Honmou et al, 1995;Taylor et al, 1998;Rho and Sankar, 1999).…”

Section: Anticonvulsant Mechanism Of Vigabatrinmentioning

confidence: 99%

GABA Transaminase Inhibition Induces Spontaneous and Enhances Depolarization-Evoked GABA Efflux via Reversal of the GABA Transporter

2001

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The GABA transporter can reverse with depolarization, causing nonvesicular GABA release. However, this is thought to occur only under pathological conditions. Patch-clamp recordings were made from rat hippocampal neurons in primary cell cultures. Inhibition of GABA transaminase with the anticonvulsant ␥-vinyl GABA (vigabatrin; 0.05-100 M) resulted in a large leak current that was blocked by bicuculline (50 M). This leak current occurred in the absence of extracellular calcium and was blocked by the GABA transporter antagonist SKF-89976a (5 M). These results indicate that vigabatrin induces spontaneous GABA efflux from neighboring cells via reversal of GABA transporters, subsequently leading to the stimulation of GABA A receptors on the recorded neuron. The leak current increased slowly over 4 d of treatment with 100 M vigabatrin, at which time it reached an equivalent conductance of 9.0 Ϯ 4.9 nS. Blockade of glutamic acid decarboxylase with semicarbazide (2 mM) decreased the leak current that was induced by vigabatrin by 47%. In untreated cells, carrier-mediated GABA efflux did not occur spontaneously but was induced by an increase in [K ϩ ] o from 3 to as little as 6 mM. Vigabatrin enhanced this depolarization-evoked nonvesicular GABA release and also enhanced the heteroexchange release of GABA induced by nipecotate. Thus, the GABA transporter normally operates near its equilibrium and can be easily induced to reverse by an increase in cytosolic [GABA] or mild depolarization. We propose that this transporter-mediated nonvesicular GABA release plays an important role in neuronal inhibition under both physiological and pathophysiological conditions and is the target of some anticonvulsants.

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“…Gabapentin is another GABAergic modulator which facilitates GABAergic neurotransmission, possibly by increasing the synthesis and nonvesicular release of GABA as well as by preventing GABA catabolism (reviewed in Taylor et al, 1998). Early studies and small-scale (9-30 patient) open outpatient trials resulted in reports of reduced cocaine cravings and use after initiation of treatment with gabapentin (Raby, 2000;Raby and Coomaraswamy, 2004;Myrick et al, 2001;Hart et al, 2004;Haney et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Effects of gabapentin on cocaine self-administration, cocaine-triggered relapse and cocaine-enhanced nucleus accumbens dopamine in rats

Peng

et al. 2008

Drug and Alcohol Dependence

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Gabapentin is a γ-aminobutyric acid (GABA) analogue, with GABAmimetic pharmacological properties. Gabapentin is used for the treatment of seizures, anxiety and neuropathic pain. It has been proposed that gabapentin may be useful in the treatment of cocaine dependence. However, clinical trials with gabapentin have shown conflicting results, while preclinical studies are sparse. In the present study, we investigated the effects of gabapentin on intravenous cocaine self-administration and cocaine-triggered reinstatement of drug-seeking behavior, as well as on cocaine-enhanced dopamine (DA) in the nucleus accumbens (NAc). We found that gabapentin (25-200 mg/kg, i.p., 30 min or 2 h prior to cocaine) failed to inhibit intravenous cocaine (0.5 mg/kg/infusion) selfadministration under a fixed-ratio reinforcement schedule or cocaine-triggered reinstatement of cocaine-seeking behavior. In vivo microdialysis showed that the same doses of gabapentin produced a modest increase (∼50%, p < 0.05) in extracellular NAc GABA levels, but failed to alter either basal or cocaine-enhanced NAc DA. These data suggest that gabapentin is a weak GABA-mimic drug. At the doses tested, it has no effect in the addiction-related animal behavioral models here tested. This

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A summary of mechanistic hypotheses of gabapentin pharmacology

Cited by 724 publications

References 90 publications

L’usage préventif de gabapentine diminue significativement la douleur postopératoire et les besoins d’analgésique de secours lors d’une cholécystectomie laparoscopique

L’usage préventif de gabapentine diminue significativement la douleur postopératoire et les besoins d’analgésique de secours lors d’une cholécystectomie laparoscopique

GABA Transaminase Inhibition Induces Spontaneous and Enhances Depolarization-Evoked GABA Efflux via Reversal of the GABA Transporter

Effects of gabapentin on cocaine self-administration, cocaine-triggered relapse and cocaine-enhanced nucleus accumbens dopamine in rats

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