Pemoline
Encyclopedia
Pemoline was first synthesized in 1913 but it's activity was not discovered until the 1930s. Under the names (Betanamin, Cylert, Tradon) it was used as a medication used to treat attention-deficit hyperactivity disorder
(ADHD) and narcolepsy
. Under the Convention on Psychotropic Substances
, it is a Schedule IV drug. It is no longer generally available in the United States. However, it can be legally prescribed in the US via the complex and rarely used "compassionate use / orphan drug" process by which a physician may complete extensive paper work on behalf of a single patient to obtain an "investigational new drug application" that allows importation and prescription of the compound on a case by case basis for up to one year and subject to renewal.
, the mechanism of action of pemoline is to inhibit the reuptake of dopamine
and to increase the levels of dopamine and norepinephrine
in the central nervous system. Pemoline has some advantages over other stimulant
s in that it does not reduce the appetite
or cause dry mouth. Dependence has only rarely been reported.
, so the FDA recommended that regular liver tests should be performed on those treated with it. Since receiving FDA approval in 1975, it has been linked with 21 cases of liver failure
, of which 13 resulted in liver replacement or death.
Although the medication was used by an estimated 10,000 Americans (mostly for narcolepsy or attention deficit disorder), in 2005 the Food and Drug Administration
(FDA) withdrew approval for pemoline due to pressure from public advocacy groups, notably Public Citizen
. Dr. Peter Lurie, deputy director of Public Citizen, had demanded that FDA summarily ban Cylert and its generic versions claiming that at least 193 children had suffered serious hepatic consequences. Under this pressure but despite the lack of evidence of serious adverse events among adults, the agency sent a letter to Abbott Laboratories
(Cylert brand owner) stating that marketing of pemoline could continue "if and only if a good faith effort is made on your part to collect the data necessary" to measure the drug's risks. In March 2005, Abbott discontinued production of Cylert, citing economic reasons.
An analogue of aminorex, 4-methylaminorex has appeared as a black market drug with abuse potential similar to methamphetamine
.
Attention-deficit hyperactivity disorder
Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and...
(ADHD) and narcolepsy
Narcolepsy
Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive sleepiness and sleep attacks at inappropriate times, such as while at work. People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia...
. Under the Convention on Psychotropic Substances
Convention on Psychotropic Substances
The Convention on Psychotropic Substances of 1971 is a United Nations treaty designed to control psychoactive drugs such as amphetamines, barbiturates, benzodiazepines, and psychedelics signed at Vienna on February 21, 1971...
, it is a Schedule IV drug. It is no longer generally available in the United States. However, it can be legally prescribed in the US via the complex and rarely used "compassionate use / orphan drug" process by which a physician may complete extensive paper work on behalf of a single patient to obtain an "investigational new drug application" that allows importation and prescription of the compound on a case by case basis for up to one year and subject to renewal.
Mechanism of action
Similar to methylphenidateMethylphenidate
Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
, the mechanism of action of pemoline is to inhibit the reuptake of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
and to increase the levels of dopamine and norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
in the central nervous system. Pemoline has some advantages over other stimulant
Stimulant
Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...
s in that it does not reduce the appetite
Anorexia (symptom)
Anorexia is the decreased sensation of appetite...
or cause dry mouth. Dependence has only rarely been reported.
Hepatotoxicity and discontinuation
In some patients pemoline is suspected of causing hepatotoxicityHepatotoxicity
Hepatotoxicity implies chemical-driven liver damage.The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Certain medicinal agents, when taken in overdoses and sometimes even when introduced within therapeutic ranges, may injure...
, so the FDA recommended that regular liver tests should be performed on those treated with it. Since receiving FDA approval in 1975, it has been linked with 21 cases of liver failure
Liver failure
Acute liver failure is the appearance of severe complications rapidly after the first signs of liver disease , and indicates that the liver has sustained severe damage . The complications are hepatic encephalopathy and impaired protein synthesis...
, of which 13 resulted in liver replacement or death.
Although the medication was used by an estimated 10,000 Americans (mostly for narcolepsy or attention deficit disorder), in 2005 the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) withdrew approval for pemoline due to pressure from public advocacy groups, notably Public Citizen
Public Citizen
Public Citizen is a non-profit, consumer rights advocacy group based in Washington, D.C., United States, with a branch in Austin, Texas. Public Citizen was founded by Ralph Nader in 1971, headed for 26 years by Joan Claybrook, and is now headed by Robert Weissman.-Lobbying Efforts:Public Citizen...
. Dr. Peter Lurie, deputy director of Public Citizen, had demanded that FDA summarily ban Cylert and its generic versions claiming that at least 193 children had suffered serious hepatic consequences. Under this pressure but despite the lack of evidence of serious adverse events among adults, the agency sent a letter to Abbott Laboratories
Abbott Laboratories
Abbott Laboratories is an American-based global, diversified pharmaceuticals and health care products company. It has 90,000 employees and operates in over 130 countries. The company headquarters are in Abbott Park, North Chicago, Illinois. The company was founded by Chicago physician, Dr....
(Cylert brand owner) stating that marketing of pemoline could continue "if and only if a good faith effort is made on your part to collect the data necessary" to measure the drug's risks. In March 2005, Abbott discontinued production of Cylert, citing economic reasons.
An analogue of aminorex, 4-methylaminorex has appeared as a black market drug with abuse potential similar to methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...
.
See also
- 4-Methylaminorex
- AminorexAminorexAminorex is an anorectic stimulant drug of the 2-amino-5-aryl oxazoline class developed by a team at McNeil in 1962. It is closely related to 4-methylaminorex. Aminorex has been shown to have locomotor stimulant effects, lying midway between dextroamphetamine and methamphetamine...
- ClominorexClominorexClominorex is a centrally acting sympathomimetic which is related to other drugs such as aminorex and pemoline. It was developed as an appetite suppressant by McNeil Laboratories in the 1950s.-See also:* 4-Methylaminorex* Aminorex* Cyclazodone...
- CyclazodoneCyclazodoneCyclazodone is a centrally acting stimulant drug developed by American Cyanamid Company in the 1960s. The drug is related to other drugs such as pemoline and 4-methylaminorex. It is a banned stimulant under the World Anti-Doping Agency prohibited list....
- FenozoloneFenozoloneFenozolone was developed by Laboratoires Dausse in the 1960s and is a psychoactive drug and stimulant related to pemoline and 4-methylaminorex which acts as a norepinephrine-dopamine releasing agent .-See also:* 4-Methylaminorex...
- FluminorexFluminorexFluminorex is a centrally acting sympathomimetic which is related to other drugs such as aminorex and pemoline. It was developed as an appetite suppressant by McNeil Laboratories in the 1950s.-See also:* 4-Methylaminorex* Aminorex* Clominorex...
- ThozalinoneThozalinoneThozalinone is a psychostimulant that has been used as an antidepressant in Europe. It has also been trialed as an anorectic. Thozalinone likely acts via inducing the release of norepinephrine and dopamine as with its analogues pemoline and aminorex.- References :...