The change in symptoms has been proposed to be due to changes in receptor sensitivity for GABA during the process of tolerance reversal. A meta-analysis found cognitive impairments in many areas due to benzodiazepine use show improvements after six months of withdrawal, but significant impairments in most areas may be permanent or may require more than six months to reverse.Protracted symptoms continue to fade over a period of many months or several years. There is no known cure for protracted benzodiazepine withdrawal syndrome except time, however, the medication flumazenil was found to be more effective than placebo in reducing feelings of hostility and aggression in patients who had been free of benzodiazepines for 4–266 weeks. This may suggest a role for flumazenil in treating protracted benzodiazepine withdrawal symptoms. Epidemiology
The severity and length of the withdrawal syndrome is likely determined by various factors, including rate of tapering, length of use and dosage size, and possible genetic factors. Those who have a prior history of withdrawing from benzodiazepines may have a sensitized or kindled central nervous system leading to worsening cognition and symptomatology, and making each subsequent withdrawal period worse. Special populations
Pediatrics
A neonatal withdrawal syndrome, sometimes severe, can occur when the mother had taken benzodiazepines, especially during the third trimester. Symptoms include hypotonia, apnoeic spells, cyanosis, impaired metabolic responses to cold stress, and seizures.
Mepivacaine  is a local anesthetic of the amide type. Mepivacaine has a reasonably rapid onset (more rapid than that of procaine) and medium duration of action (shorter than that of procaine) and is marketed under various trade names including Carbocaine and Polocaine. Mepivacaine became available in the United States in the 1960s. Mepivacaine is used in any infiltration and local anesthesia. It is supplied as the hydrochloride salt of the racemate, which consists of R(-)-mepivacaine and S(+)-mepivacaine in equal proportions. These two enantiomers have markedly different pharmacokinetic properties.Mepivacaine was originally synthesized in Sweden at the laboratory of Bofors Nobelkrut in 1956. References
External links
Mepivacaine at RxList