Gabapentin: can it be misused?

Gabapentin, a gamma-aminobutyric acid analog drug, appears to be safe and efficacious for the treatment of alcohol dependence. Gabapentin is not a controlled drug, but there are anecdotal reports of its misuse and abuse as well as reports of withdrawal symptoms associated with abrupt discontinuation. The risk of gabapentin misuse is inconsistent, the magnitude of the risk is small, and the risk is not comparable to the much higher risks associated with alcohol use; benzodiazepine, opioid, and stimulant drug use; or illicit drug use. Reports of gabapentin misuse are not unique to this drug, as misuse of prescription medications not typically considered "drugs of abuse" can also occur.

Schedules of controlled substances: placement of pregabalin into schedule V. Final rule.

This final rule is issued by the Deputy Administrator of the Drug Enforcement Administration (DEA) to place the substance pregabalin [(S)-3-(aminomethyl)-5-methylhexanoic acid], including its salts, and all products containing pregabalin into Schedule V of the Controlled Substances Act (CSA). As a result of this rule, the regulatory controls and criminal sanctions of Schedule V will be applicable to the manufacture, distribution, dispensing, importation and exportation of pregabalin and products containing pregabalin.

Expression of glutamate transporter, GABRA6, serine proteinase inhibitor 2 and low levels of glutamate and GABA in the brain of knock-out mouse for Canavan disease.

Canavan disease (CD) is an autosomal recessive leukodystrophy characterized by spongy degeneration of the brain. The clinical features of CD are hypotonia, megalencephaly, and mental retardation leading to early death. While aspartoacylase (ASPA) activity increases with age in the wild type mouse brain, there is no ASPA activity in the CD mouse brain. So far ASPA deficiency and elevated NAA have been ascribed with the CD. Other factors affecting the brain that result from ASPA deficiency may lead pathophysiology of CD. The NMR spectra and amino acid analysis showed lower levels of glutamate and gamma-aminobutyric acid in the CD mouse brain compared to the wild type. Microarray gene expression on CD mouse brain showed glutamate transporter-EAAT4 and gamma-aminobutyric acid-A receptor, subunit alpha6 (GABRA6) were lower 9.7- and 119.1-fold, respectively. Serine proteinase inhibitor 2 (Spi2) was 29.9-fold higher in the CD mouse brain compared to the wild type. The decrease of GABRA6 and high expression of Spi2 in CD mouse brain were also confirmed by real-time RT-PCR. This first report showing abnormal expression of EAAT4, GABRA6, Spi2 combined with lower levels of glutamate and GABA are likely to be associated with the pathophysiology of CD.

Central nervous system supersensitivity and withdrawal from long-term treatment with barbital

The effects of withdrawal from long-term treatment with increasing concentrations of sodium barbital in the drinking water were studied in rats. Animals were tested 72 h after the removal of the drug. Withdrawal of barbital induced a significant leftward displacement of the dose-response curves obtained for the convulsive effects of strychnine, picrotoxin and 3-mercaptopropionic acid. The removal of the drug also made the rats more sensitive to convulsions elicited by sound. Baclofen and THIP were able to decrease the audiogenic response score of rats, withdrawn from barbital, in a dose-dependent way. These effects were interpreted to be a consequence of changes in the sensitivity of central GABA(A) and/or noradrenergic receptors induced by depression due to long-term administration of barbital.