Alpidem
Encyclopedia
Alpidem is an anxiolytic
drug from the imidazopyridine
family, related to the more well known sleeping medication zolpidem
. Unlike zolpidem however, alpidem does not produce sedative
effects at normal doses, and is instead used specifically for the treatment of anxiety
.
Alipidem was developed by Synthélabo (now part of Sanofi-Aventis
). It was approved for marketing in France in 1991. Clinical trial to obtain US FDA approval were halted in 1992 and the drug never received FDA approval. It was withdrawn from the French market by 1994 and is not approved for marketing anywhere in the world.
Alpidem was known to act selectively on the α3 receptor subtype and to a lesser extent at the α1 subtype (Kd of 0.33nM and 1.67nM respectively), of the benzodiazepine
receptor. However the chemical structure
of alpidem is not related to that of the benzodiazepines, and alpidem is thus sometimes referred to as a nonbenzodiazepine
.
. Most of these patients had exhibited either sensitivity
or resistance
to benzodiazepine
therapy, and therefore switched to a non-benzodiazepine medication due to the reduced incidence of side effects relative to benzodiazepine drugs. Alpidem produced little or no sedative
or hypnotic
action at normal doses but may have produced sedation when used at a high dose, and only had anticonvulsant
actions at much higher doses than those used clinically for the treatment of anxiety.
.
Anxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
drug from the imidazopyridine
Imidazopyridine
The imidazopyridines are a class of drugs defined by their chemical structure. They are generally GABAA receptor agonists, however recently proton pump inhibitors in this class have been developed as well. Despite usually being similar to them in effect, they are not chemically related to...
family, related to the more well known sleeping medication zolpidem
Zolpidem
Zolpidem is a prescription medication used for the short-term treatment of insomnia, as well as some brain disorders. It is a short-acting nonbenzodiazepine hypnotic of the imidazopyridine class that potentiates gamma-aminobutyric acid , an inhibitory neurotransmitter, by binding to GABAA...
. Unlike zolpidem however, alpidem does not produce sedative
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
effects at normal doses, and is instead used specifically for the treatment of anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
.
Alipidem was developed by Synthélabo (now part of Sanofi-Aventis
Sanofi-Aventis
Sanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...
). It was approved for marketing in France in 1991. Clinical trial to obtain US FDA approval were halted in 1992 and the drug never received FDA approval. It was withdrawn from the French market by 1994 and is not approved for marketing anywhere in the world.
Alpidem was known to act selectively on the α3 receptor subtype and to a lesser extent at the α1 subtype (Kd of 0.33nM and 1.67nM respectively), of the benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
receptor. However the chemical structure
Chemical structure
A chemical structure includes molecular geometry, electronic structure and crystal structure of molecules. Molecular geometry refers to the spatial arrangement of atoms in a molecule and the chemical bonds that hold the atoms together. Molecular geometry can range from the very simple, such as...
of alpidem is not related to that of the benzodiazepines, and alpidem is thus sometimes referred to as a nonbenzodiazepine
Nonbenzodiazepine
The nonbenzodiazepines, also called benzodiazepine-like drugs, are a class of psychoactive drugs pharmacologically resembling the benzodiazepines, with similar benefits, side effects and risks, despite having dissimilar or entirely different chemical structures.-Classes:There are currently three...
.
Use prior to removal from market
Alpidem was generally prescribed to patients with moderate to severe anxietyAnxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
. Most of these patients had exhibited either sensitivity
Stimulus (physiology)
In physiology, a stimulus is a detectable change in the internal or external environment. The ability of an organism or organ to respond to external stimuli is called sensitivity....
or resistance
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...
to benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
therapy, and therefore switched to a non-benzodiazepine medication due to the reduced incidence of side effects relative to benzodiazepine drugs. Alpidem produced little or no sedative
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
or hypnotic
Hypnotic
Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...
action at normal doses but may have produced sedation when used at a high dose, and only had anticonvulsant
Anticonvulsant
The anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
actions at much higher doses than those used clinically for the treatment of anxiety.
Dangers
In 1996, Alpidem was withdrawn from the market in most of the world following reports of severe liver damageHepatotoxicity
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...
.
See also
- ZolpidemZolpidemZolpidem is a prescription medication used for the short-term treatment of insomnia, as well as some brain disorders. It is a short-acting nonbenzodiazepine hypnotic of the imidazopyridine class that potentiates gamma-aminobutyric acid , an inhibitory neurotransmitter, by binding to GABAA...
- AnxiolyticAnxiolyticAn anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
- Benzodiazepine (receptor)BenzodiazepineA benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
- ImidazopyridineImidazopyridineThe imidazopyridines are a class of drugs defined by their chemical structure. They are generally GABAA receptor agonists, however recently proton pump inhibitors in this class have been developed as well. Despite usually being similar to them in effect, they are not chemically related to...
s