Research and Clinical Trials on Gabapentin (Neurontin, Gabarone)

By Dr Greg Mulhauser
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This list of current clinical research trials on Gabapentin (Neurontin, Gabarone) is followed by a short set of abstracts from the most recent research articles published on the drug.

Article Contents

Gabapentin (Neurontin, Gabarone) Clinical Research Trials

From our searchable database at ClinicalTrialsFeeds.org, this list includes all the latest information about clinical trials involving Gabapentin (Neurontin, Gabarone).

 

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Current Research Literature on Gabapentin (Neurontin, Gabarone)

Here are abstracts for some of the latest research articles to have appeared on Gabapentin (Neurontin, Gabarone):

Multiple Conformational States in Crystals and in Solution in alphagamma Hybrid Peptides. Fragility of the C12 Helix in Short Sequences.

J Org Chem. 2008 Jul 29;
Chatterjee S, Vasudev PG, Ananda K, Raghothama S, Shamala N, Balaram P
The conformational properties of foldamers generated from alphagamma hybrid peptide sequences have been probed in the model sequence Boc-Aib-Gpn-Aib-Gpn-NHMe. The choice of alpha-aminoisobutyryl (Aib) and gabapentin (Gpn) residues greatly restricts sterically accessible conformational space. This model sequence was anticipated to be a short segment of the alphagamma C 12 helix, stabilized by three successive 4-->1 hydrogen bonds, corresponding to a backbone-expanded analogue of the alpha polypeptide 3 10-helix. Unexpectedly, three distinct crystalline polymorphs were characterized in the solid state by X-ray diffraction. In one form, two successive C 12 hydrogen bonds were obtained at the N-terminus, while a novel C 17 hydrogen-bonded gammaalphagamma turn was observed at the C-terminus. In the other two polymorphs, isolated C 9 and C 7 hydrogen-bonded turns were observed at Gpn (2) and Gpn (4). Isolated C 12 and C 9 turns were also crystallographically established in the peptides Boc-Aib-Gpn-Aib-OMe and Boc-Gpn-Aib-NHMe, respectively. Selective line broadening of NH resonances and the observation of medium range NH(i) NH( i+2) NOEs established the presence of conformational heterogeneity for the tetrapeptide in CDCl 3 solution. The NMR results are consistent with the limited population of the continuous C 12 helix conformation. Lengthening of the (alphagamma) n sequences in the nonapeptides Boc-Aib-Gpn-Aib-Gpn-Aib-Gpn-Aib-Gpn-Xxx (Xxx = Aib, Leu) resulted in the observation of all of the sequential NOEs characteristic of an alphagamma C 12 helix. These results establish that conformational fragility is manifested in short hybrid alphagamma sequences despite the choice of conformationally constrained residues, while stable helices are formed on chain extension.

Pharmacokinetic role of L-type amino acid transporters LAT1 and LAT2.

Eur J Pharm Sci. 2008 Jul 5;
Del Amo EM, Urtti A, Yliperttula M
LAT1 and LAT2 are heterodimeric large amino acid transporters that are expressed in various tissues, including the intestinal wall, blood-brain barrier, and kidney. These transporters consist of membrane spanning light chain and heavy chain, and they act as 1:1 exchangers in concert with other amino acid transporters. Only a few drugs (less than 10) are substrates of LAT1 and LAT2, including l-DOPA, alpha-methyldopa, melphalan, and gabapentin. The mechanisms and substrates have been mostly elucidated using mammalian cells and Xenopus oocytes. The in vivo relevance of LAT1 and LAT2 in pharmacokinetics is obscure, because contradictory findings have been reported. It is difficult to make quantitative pharmacokinetic conclusions about LAT1 and LAT2. This is due to the possible involvement of other transporters (including cross-linked heterodimers of light chain with different heavy chains, other overlapping transporters, for example TAT1), competing endogenous amino acids, and saturation phenomena. This review presents the current functional knowledge on LAT1 and LAT2 with emphasis on their potential involvement in pharmacokinetics.

[Restless-legs syndrome.]

Rev Neurol (Paris). 2008 Jul 23;
Karroum E, Konofal E, Arnulf I
Restless-legs syndrome (RLS) is a sensorimotor disorder, characterized by an irresistible urge to move the legs usually accompanied or caused by uncomfortable and unpleasant sensations. It begins or worsens during periods of rest or inactivity, is partially or totally relieved by movements and is exacerbated or occurs at night and in the evening. RLS sufferers represent 2 to 3% of the general population in Western countries. Supportive criteria include a family history, the presence of periodic-leg movements (PLM) when awake or asleep and a positive response to dopaminergic treatment. The RLS phenotypes include an early onset form, usually idiopathic with a familial history and a late onset form, usually secondary to peripheral neuropathy. Recently, an atypical RLS phenotype without PLM and l-DOPA resistant has been characterized. RLS can occur in childhood and should be distinguished from attention deficit/hyperactivity disorder, growing pains and sleep complaints in childhood. RLS should be included in the diagnosis of all patients consulting for sleep complaints or discomfort in the lower limbs. It should be differentiated from akathisia, that is, an urge to move the whole body without uncomfortable sensations. Polysomnographic studies and the suggested immobilization test can detect PLM. Furthermore, an l-DOPA challenge has recently been validated to support the diagnosis of RLS. RLS may cause severe-sleep disturbances, poor quality of life, depressive and anxious symptoms and may be a risk factor for cardiovascular disease. In most cases, RLS is idiopathic. It may also be secondary to iron deficiency, end-stage renal disease, pregnancy, peripheral neuropathy and drugs, such as antipsychotics and antidepressants. The small-fiber neuropathy can mimic RLS or even trigger it. RLS is associated with many neurological and sleep disorders including Parkinson's disease, but does not predispose to these diseases. The pathophysiology of RLS includes an altered brain-iron metabolism, a dopaminergic dysfunction, a probable role of pain control systems and a genetic susceptibility with nine loci and three polymorphisms in genes serving developmental functions. RLS treatment begins with the elimination of triggering factors and iron supplementation when deficient. Mild or intermittent RLS is usually treated with low doses of l-DOPA or codeine; the first-line treatment for moderate to severe RLS is dopaminergic agonists (pramipexole, ropinirole, rotigotine). In severe, refractory or neuropathy-associated RLS, antiepileptic (gabapentin, pregabalin) or opioid (oxycodone, tramadol) drugs can be used.

Pain relief by gabapentin and pregabalin via supraspinal mechanisms after peripheral nerve injury.

J Neurosci Res. 2008 Jul 24;
Tanabe M, Takasu K, Takeuchi Y, Ono H
The antihypersensitivity actions of gabapentin and pregabalin have been well characterized in a large number of studies, although the underlying mechanisms have yet to be defined. We have been focusing on the supraspinal structure as a possible site for their action and have demonstrated that intracerebroventricular (i.c.v.) administration of gabapentin and pregabalin indeed decreases thermal and mechanical hypersensitivity in a murine chronic pain model involving partial ligation of the sciatic nerve. This novel supraspinally mediated analgesic effect was markedly suppressed by either depletion of central noradrenaline (NA) or blockade of spinal alpha(2)-adrenergic receptors. Moreover, i.c.v. injection of gabapentin and pregabalin increased spinal NA turnover in mice only after peripheral nerve injury. In locus coeruleus (LC) neurons in brainstem slices prepared from mice after peripheral nerve injury, gabapentin reduced the gamma-aminobutyric acid (GABA) type A receptor-mediated inhibitory postsynaptic currents (IPSCs). Glutamate-mediated excitatory synaptic transmission was hardly affected. Moreover, gabapentin did not reduce IPSCs in slices taken from mice given a sham operation. Although gabapentin altered neither the amplitude nor the frequency of miniature IPSCs, it reduced IPSCs together with an increase in the paired-pulse ratio, suggesting that gabapentin acts on the presynaptic GABAergic nerve terminals in the LC. Together, the data suggest that gabapentin presynaptically reduces GABAergic synaptic transmission, thereby removing the inhibitory influence on LC neurons only in neuropathic pain states, leading to activation of the descending noradrenergic system. (c) 2008 Wiley-Liss, Inc.

Anticonvulsants to treat idiopathic restless legs syndrome: systematic review.

Arq Neuropsiquiatr. 2008 Jun; 66(2b): 431-435
Conti CF, Oliveira MM, Valbuza JS, Prado LB, Carvalho LB, Prado GF
BACKGROUND: Restless legs syndrome (RLS) is a sensory motor disorder characterized by a distressing urge to move the legs and sometimes also other parts of the body usually accompanied by a marked sense of discomfort or pain in the leg or other affected body part. Many treatments have been used to minimize the discomfort of the disease, among them the anticonvulsant therapy. AIM: This review aims to evaluate the efficacy and safety of anticonvulsant treatment for idiopathic RLS. METHOD: Systematic review of randomized or quasi-randomized, double blind trials on anticonvulsant treatment for RLS. Outcomes: relief of RLS symptoms, subjective and objective sleep quality, quality of life, and adverse events associated with the treatments. RESULTS: A total of 231 patients were randomized in three cross over studies and one parallel study. Three studies with carbamazepine, one with sodium valproate, and one with gabapentin, and they were very heterogeneous so we could not perform a metanalyses. CONCLUSIONS: There is no scientific evidence on RLS treatment with anticonvulsants for clinical practice.

 

This page was last reviewed by Dr Greg Mulhauser, Friday, 4 July 2008.

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