Cycloserine
Encyclopedia
Cycloserine is an antibiotic
effective against Mycobacterium tuberculosis
. For the treatment of tuberculosis, it is classified as a second line drug, i.e. its use is only considered if one or more first line drugs cannot be used.
Although in principle active against other bacteria as well, cycloserine is not commonly used in the treatment of infections other than tuberculosis.
; the two residues are joined by D-alanine ligase. Both enzymes are competitively inhibited by cycloserine.
to exposure therapy
for anxiety disorders (e.g. phobias), depression
, obsessive-compulsive disorder
and schizophrenia
. It has been experimentally used for treatment of Gaucher's disease
.
Recent research suggests that D-cycloserine (d-4-amino-3-isoxazolidinone) may be effective in treating chronic pain.
The side effects are mainly central nervous system (CNS) manifestations, i.e. headache
, irritability, depression
, psychosis
convulsions. Co-administration of pyridoxine
can reduce the incidence of some of the CNS side effects (e.g. convulsions).
These psychotropic responses are related to D-cycloserine's action as a partial agonist
of the neuronal NMDA receptor
for glutamate and have been examined in implications with sensory-related fear extinction
in the amygdala
, and extinction
of cocaine
seeking in the nucleus accumbens
.
D-cycloserine is a partial agonist
at the glycine receptor
, and has been shown to have cognition-enhancing properties for models of Parkinsons disease in primates.
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
effective against Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...
. For the treatment of tuberculosis, it is classified as a second line drug, i.e. its use is only considered if one or more first line drugs cannot be used.
Although in principle active against other bacteria as well, cycloserine is not commonly used in the treatment of infections other than tuberculosis.
Mode of action
The terminal two amino acid residues of the murein precursor lipid II consist of D-alanine, which is produced by the enzyme alanine racemaseAlanine racemase
In enzymology, an alanine racemase is an enzyme that catalyzes the chemical reactionHence, this enzyme has one substrate, L-alanine, and one product, D-alanine....
; the two residues are joined by D-alanine ligase. Both enzymes are competitively inhibited by cycloserine.
Applications and side effects unrelated to antibiotic activity
It is also being trialed as an adjuvantAdjuvant
An adjuvant is a pharmacological or immunological agent that modifies the effect of other agents, such as a drug or vaccine, while having few if any direct effects when given by itself...
to exposure therapy
Exposure therapy
Exposure therapy is a technique in behavior therapy intended to treat anxiety disorders and involves the exposure to the feared object or context without any danger in order to overcome their anxiety. Procedurally it is similar to the fear extinction paradigm in rodent work...
for anxiety disorders (e.g. phobias), depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
, obsessive-compulsive disorder
Obsessive-compulsive disorder
Obsessive–compulsive disorder is an anxiety disorder characterized by intrusive thoughts that produce uneasiness, apprehension, fear, or worry, by repetitive behaviors aimed at reducing the associated anxiety, or by a combination of such obsessions and compulsions...
and schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
. It has been experimentally used for treatment of Gaucher's disease
Gaucher's disease
Gaucher's disease is a genetic disease in which a fatty substance accumulates in cells and certain organs.Gaucher's disease is the most common of the lysosomal storage diseases. It is caused by a hereditary deficiency of the enzyme glucosylceramidase. The enzyme acts on the fatty acid...
.
Recent research suggests that D-cycloserine (d-4-amino-3-isoxazolidinone) may be effective in treating chronic pain.
The side effects are mainly central nervous system (CNS) manifestations, i.e. headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, irritability, depression
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
, psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
convulsions. Co-administration of pyridoxine
Pyridoxine
Pyridoxine is one of the compounds that can be called vitamin B6, along with pyridoxal and pyridoxamine. It differs from pyridoxamine by the substituent at the '4' position. It is often used as 'pyridoxine hydrochloride'.-Chemistry:...
can reduce the incidence of some of the CNS side effects (e.g. convulsions).
These psychotropic responses are related to D-cycloserine's action as a partial agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
of the neuronal NMDA receptor
NMDA receptor
The NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
for glutamate and have been examined in implications with sensory-related fear extinction
Extinction (psychology)
Extinction is the conditioning phenomenon in which a previously learned response to a cue is reduced when the cue is presented in the absence of the previously paired aversive or appetitive stimulus.-Fear conditioning:...
in the amygdala
Amygdala
The ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-...
, and extinction
Extinction (psychology)
Extinction is the conditioning phenomenon in which a previously learned response to a cue is reduced when the cue is presented in the absence of the previously paired aversive or appetitive stimulus.-Fear conditioning:...
of cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
seeking in the nucleus accumbens
Nucleus accumbens
The nucleus accumbens , also known as the accumbens nucleus or as the nucleus accumbens septi , is a collection of neurons and forms the main part of the ventral striatum...
.
D-cycloserine is a partial agonist
Partial agonist
Partial agonists bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist...
at the glycine receptor
Glycine receptor
The glycine receptor, or GlyR, is the receptor for the amino acid neurotransmitter glycine. GlyR is an ionotropic receptor that produces its effects through chloride current...
, and has been shown to have cognition-enhancing properties for models of Parkinsons disease in primates.