Пемолин: Қолданылуы, қауіптері және ескертулер

Stimulant, used in the treatment of ADHD
Drugbox
| Verifiedfields = changed
| verifiedrevid = 461086403
| IUPAC name = (RS) 2 amino 5 phenyl 1,3 oxazol 4(5H) one
| image = Pemoline structure 2. svg
| width = 175px
| image2 = File:Pemoline ball and stick model. png
| width2 = 175px
| chirality = Racemic mixture

| tradename = Cylert, others
| Drugs. com =
| pregnancy US = B
| legal AU = S4
| legal BR = B1
| legal BR comment =
| legal CA = Schedule IV
| legal DE = Rx only/Anlage III
| legal US = Schedule IV
| routes of administration = Oral The medication was taken by mouth. Pemoline is a psychostimulant and acts as a selective dopamine reuptake inhibitor and releasing agent. The medication was typically used at doses of 18.75 to 112.5mg once per day in the treatment of ADHD, with the effective dose for most people being in the range of 56.25 to 75mg.

Rarely, pemoline is implicated in causing hepatotoxicity. Because of this, the FDA recommended that regular liver tests be performed in those treated with it. Since being introduced, it has been linked with at least 21 cases of liver failure, of which 13 resulted in liver replacement or death. Approximately 1–2% of patients taking the drug show elevated levels of liver transaminase enzymes, a marker for liver toxicity, though serious cases are rare. Over 200,000 children with ADHD were prescribed pemoline in the United States and Canada alone during the approximate 25 years that it was available, plus a smaller number of adults prescribed it for other indications (and not including prescriptions in the rest of the world). As such, the number of liver failure cases was statistically not that large. However the reactions proved idiosyncratic and unpredictable, with patients sometimes taking the drug with no issue for months or even years, before suddenly developing severe liver toxicity. There was no clear exposure–toxicity relationship, and no characteristic liver pathology findings. Some patients showed as little as one week between first appearance of jaundice and complete liver failure, and some of the patients that developed liver failure had not showed elevated liver transaminase levels when tested previously. On the other hand, there are no cases of liver failure associated with pemoline in Japan, although it is used at lower doses and is only prescribed for the niche indication of narcolepsy in this country.

Other stimulants and monoamine oxidase inhibitors are contraindicated with pemoline.

The pharmacodynamics of pemoline are poorly understood and its precise mechanism of action hasn't been definitively determined. However, pemoline has similar activity and effects to those of other psychostimulants, and in animals the medication appears to act as a dopamine reuptake inhibitor and releasing agent. In contrast to most other stimulants, pemoline appears to produce no significant central or peripheral noradrenergic effects. Peak levels have been reported to be in the range of 2 to 4.5μg/mL. Others such as lanthanide pemoline salts such as pemoline cerium can be prepared; pemoline beryllium would presumably be toxic.

Pemoline was first synthesized in 1913 but its activity was not discovered until the 1930s. Pemoline was approved for the treatment of ADHD in the United States in 1975. However, findings suggested that clinicians poorly followed the FDA's directives on use of pemoline. It remains available in Japan for the treatment of narcolepsy as of 2017.

Under the Convention on Psychotropic Substances, it is a schedule IV controlled substance. Pemoline is Schedule IV Non Narcotic (Stimulant) controlled substance with a DEA ACSCN of 1530 and is not subject to annual manufacturing quotas.