Reuptake inhibitor
Encyclopedia
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
that inhibits the plasmalemmal transporter
Transporter
Transporter may refer to:* Transporter , types of vehicles designed to transport items* Volkswagen Transporter, a model of van- Film and television :...
-mediated reuptake
Reuptake
Reuptake, or re-uptake, is the reabsorption of a neurotransmitter by a neurotransmitter transporter of a pre-synaptic neuron after it has performed its function of transmitting a neural impulse....
of a neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
from the synapse
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
into the pre-synaptic neuron
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
, leading to an increase in the extracellular
Extracellular
In cell biology, molecular biology and related fields, the word extracellular means "outside the cell". This space is usually taken to be outside the plasma membranes, and occupied by fluid...
concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...
s of the neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
and therefore an increase in neurotransmission
Neurotransmission
Neurotransmission , also called synaptic transmission, is the process by which signaling molecules called neurotransmitters are released by a neuron , and bind to and activate the receptors of another neuron...
.
Many drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
s utilize reuptake inhibition to exert their psychological and physiological effects, including various antidepressants, anxiolytic
Anxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
s, 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, and anorectic
Anorectic
An anorectic or anorexic , also known as anorexigenic or appetite suppressant, is a dietary supplement and/or drug which reduces appetite, food consumption, and as a result, causes weight loss to occur.-List of anorectics:Numerous pharmaceutical compounds are marketed as appetite suppressants.The...
s, among others. Most known reuptake inhibitors affect the monoamine neurotransmitter
Monoamine neurotransmitter
thumb|right|350px| A phylogenetic tree showing how a number of monoamine receptors are related to each other.Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group that is connected to an aromatic ring by a two-carbon chain...
s serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
, and 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...
. There are also a number of pharmaceutical drugs and research chemicals that act as reuptake inhibitors for other neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
s such as adenosine, GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
, glutamate, and the endocannabinoids as well.
Active site transporter substrates
Competitive inhibition
Competitive inhibition is a form of enzyme inhibition where binding of the inhibitor to the active site on the enzyme prevents binding of the substrate and vice versa.-Mechanism:...
substrate
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
s that work by binding
Binding (molecular)
Molecular binding is an attractive interaction between two molecules which results in a stable association in which the molecules are in close proximity to each other...
directly to the plasmalemma transporter of the neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
in question. They occupy
Receptor theory
Receptor theory is the application of receptor models to explain drug behaviour. Pharmacological receptor models preceded accurate knowledge of receptors by many years. John Newport Langley and Paul Ehrlich introduced the concept of a receptor that would mediate drug action at the beginning of the...
the transporter in place of the respective neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
and competitively
Competitive inhibition
Competitive inhibition is a form of enzyme inhibition where binding of the inhibitor to the active site on the enzyme prevents binding of the substrate and vice versa.-Mechanism:...
block
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
it from being transported
Active transport
Active transport is the movement of a substance against its concentration gradient . In all cells, this is usually concerned with accumulating high concentrations of molecules that the cell needs, such as ions, glucose, and amino acids. If the process uses chemical energy, such as from adenosine...
from the nerve terminal or synapse
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
into the pre-synaptic
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
. With high enough doses, occupation
Receptor theory
Receptor theory is the application of receptor models to explain drug behaviour. Pharmacological receptor models preceded accurate knowledge of receptors by many years. John Newport Langley and Paul Ehrlich introduced the concept of a receptor that would mediate drug action at the beginning of the...
becomes as much as 80-90%. At this level of inhibition, the transporter will be considerably less efficient at removing excess neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
from the synapse
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
and this causes a substantial increase in the extracellular
Extracellular
In cell biology, molecular biology and related fields, the word extracellular means "outside the cell". This space is usually taken to be outside the plasma membranes, and occupied by fluid...
concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...
s of the neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
and therefore an increase in overall neurotransmission
Neurotransmission
Neurotransmission , also called synaptic transmission, is the process by which signaling molecules called neurotransmitters are released by a neuron , and bind to and activate the receptors of another neuron...
.
Allosteric site transporter substrates
Binding (molecular)
Molecular binding is an attractive interaction between two molecules which results in a stable association in which the molecules are in close proximity to each other...
to allosteric sites and inhibit reuptake
Reuptake
Reuptake, or re-uptake, is the reabsorption of a neurotransmitter by a neurotransmitter transporter of a pre-synaptic neuron after it has performed its function of transmitting a neural impulse....
indirectly and noncompetitively
Non-competitive inhibition
Non-competitive inhibition is a type of enzyme inhibition where the inhibitor reduces the activity of the enzyme, by binding not to the active site on the enzyme, but to a different site...
.
Phencyclidine
Phencyclidine
Phencyclidine , commonly initialized as PCP and known colloquially as angel dust, is a recreational dissociative drug...
and related drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
s such as benocyclidine
Benocyclidine
Benocyclidine , or benzothiophenylcyclohexylpiperidine , is a psychoactive drug and research chemical of the arylcyclohexylamine and piperidine chemical classes. It acts a potent and selective dopamine reuptake inhibitor and a stimulant...
, tenocyclidine
Tenocyclidine
Tenocyclidine is a dissociative anesthetic drug with stimulant and hallucinogenic effects. It is similar in effects to phencyclidine but is considerably more potent. TCP has slightly different binding properties to PCP, with more affinity for the NMDA receptors, but less affinity for the sigma...
, ketamine
Ketamine
Ketamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist...
, and dizocilpine
Dizocilpine
Dizocilpine , also known as MK-801, is a non-competitive antagonist of the N-methyl-d-aspartate receptor, a glutamate receptor. Glutamate is the brain's primary excitatory neurotransmitter...
(MK-801), have been shown to inhibit the reuptake of the monoamine neurotransmitter
Monoamine neurotransmitter
thumb|right|350px| A phylogenetic tree showing how a number of monoamine receptors are related to each other.Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group that is connected to an aromatic ring by a two-carbon chain...
s. They appear to exert their reuptake inhibition by binding to vaguely characterized allosteric sites on each of the respective monoamine transporter
Monoamine transporter
Monoamine transporters are protein structures that function as integral plasma membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. Three major classes of MATs are responsible for the reuptake of their associated amine neurotransmitters...
s. Benztropine
Benztropine
Benzatropine , also known as benztropine , is an anticholinergic marketed under the trade name Cogentin which is used in the treatment of Parkinson's disease, parkinsonism, akathisia, and dystonia.- Indications :...
, fluoxetine
Fluoxetine
Fluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...
, mazindol
Mazindol
Mazindol is a stimulant drug of the tetracyclic chemical class which is used as an anorectic. It was developed by Sandoz-Wander in the 1960s- Indications :...
, and vanoxerine
Vanoxerine
Vanoxerine is a piperazine derivative which is a potent and selective DRI. GBR-12909 binds to the target site on the DAT ~ 500 times more strongly than cocaine, but simultaneously inhibits the release of dopamine...
also bind to these sites and have similar properties. In addition to their high affinity for the main site
Active site
In biology the active site is part of an enzyme where substrates bind and undergo a chemical reaction. The majority of enzymes are proteins but RNA enzymes called ribozymes also exist. The active site of an enzyme is usually found in a cleft or pocket that is lined by amino acid residues that...
of the monoamine transporters, several competitive
Competitive inhibition
Competitive inhibition is a form of enzyme inhibition where binding of the inhibitor to the active site on the enzyme prevents binding of the substrate and vice versa.-Mechanism:...
transporter substrate
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
s such as 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...
and indatraline
Indatraline
Indatraline is a non-selective monoamine transporter inhibitor that has been shown to block the reuptake of dopamine, norepinephrine, and serotonin with effects similar to those of cocaine...
have lower affinity for these allosteric sites as well.
A few of the selective serotonin reuptake inhibitor
Selective serotonin reuptake inhibitor
Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed...
s (SSRIs) such as fluoxetine
Fluoxetine
Fluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...
and the dextro-enantiomer
Enantiomer
In chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...
of citalopram
Citalopram
Citalopram brand names: Celexa, Cipramil) is an antidepressant drug of the selective serotonin reuptake inhibitor class. It has U.S...
appear to be allosteric serotonin reuptake inhibitor
Allosteric serotonin reuptake inhibitor
Allosteric serotonin reuptake inhibitor is a marketing classification invented by the pharmaceutical company Lundbeck for its selective serotonin reuptake inhibitor escitalopram, the S stereoisomer of the SSRI citalopram...
s. Instead of binding to the active site on the serotonin transporter
Serotonin transporter
The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...
, they bind to an allosteric site, which exerts its effects by causing conformational change
Conformational change
A macromolecule is usually flexible and dynamic. It can change its shape in response to changes in its environment or other factors; each possible shape is called a conformation, and a transition between them is called a conformational change...
s in the transporter protein, and thereby modulating the affinity of substrates for the active site. As a result, escitalopram
Escitalopram
Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor class. It is approved by the U.S...
has been marketed
Marketing
Marketing is the process used to determine what products or services may be of interest to customers, and the strategy to use in sales, communications and business development. It generates the strategy that underlies sales techniques, business communication, and business developments...
as an allosteric serotonin reuptake inhibitor
Allosteric serotonin reuptake inhibitor
Allosteric serotonin reuptake inhibitor is a marketing classification invented by the pharmaceutical company Lundbeck for its selective serotonin reuptake inhibitor escitalopram, the S stereoisomer of the SSRI citalopram...
. Notably, this allosteric site may be directly related to the above-mentioned PCP
Phencyclidine
Phencyclidine , commonly initialized as PCP and known colloquially as angel dust, is a recreational dissociative drug...
binding site
Binding site
In biochemistry, a binding site is a region on a protein, DNA, or RNA to which specific other molecules and ions—in this context collectively called ligands—form a chemical bond...
s.
Two of the primary active constituents of the medicinal herb Hypericum perforatum (St. John's Wort) are hyperforin
Hyperforin
Hyperforin is a phytochemical produced by some of the members of the plant genus Hypericum, notably Hypericum perforatum .- Occurrence :...
and adhyperforin
Adhyperforin
Adhyperforin is a phytochemical found in the members of the plant genus Hypericum including St. John's Wort. It has a very similar pharmacological profile to hyperforin and acts as a TRPC6 ion channel activator, thereby inhibiting the reuptake of various neurotransmitters including serotonin,...
. Hyperforin and adhyperforin are inhibitors of the reuptake of serotonin, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
, 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...
, GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
, and glutamate, and they exert these effects allosterically by binding to and activating
Receptor theory
Receptor theory is the application of receptor models to explain drug behaviour. Pharmacological receptor models preceded accurate knowledge of receptors by many years. John Newport Langley and Paul Ehrlich introduced the concept of a receptor that would mediate drug action at the beginning of the...
the transient receptor potential
Transient receptor potential
Transient receptor potential channels are a group of ion channels located mostly on the plasma membrane of numerous human and animal cell types. There are about 28 TRP channels that share some structural similarity to each other...
cation channel TRPC6
TRPC6
Transient receptor potential cation channel, subfamily C, member 6, also known as TRPC6, is a human gene encoding a protein of the same name. TRPC6 is a transient receptor potential ion channel...
. Activation of TRPC6 induces the entry of calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
(Ca2+) and sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
(Na+) into the cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
, which causes the effect.
Vesicular transporter substrates
Active transport
Active transport is the movement of a substance against its concentration gradient . In all cells, this is usually concerned with accumulating high concentrations of molecules that the cell needs, such as ions, glucose, and amino acids. If the process uses chemical energy, such as from adenosine...
, and block
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
s the intracellular
Intracellular
Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...
repackaging
Active transport
Active transport is the movement of a substance against its concentration gradient . In all cells, this is usually concerned with accumulating high concentrations of molecules that the cell needs, such as ions, glucose, and amino acids. If the process uses chemical energy, such as from adenosine...
of neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
s into cytoplasmic vesicles. In contrast to plasmalemmal reuptake inhibitors, vesicular reuptake inhibitors do not increase the synaptic
Synaptic
Synaptic may refer to:*Synapse, part of the nervous system*Synapsis, the pairing of two homologous chromosomes*Synaptic , a Linux graphical package management program for APT See also...
concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...
s of a neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
, only the cytoplasmic concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...
s; unless, that is, they also act as plasmalemmal transporter reverser
Transporter reversal
Transporter reversal is the action of reversing a plasmalemmal transporter via a process known as phosphorylation. Neurotransmitter transporters normally function as part of the reuptake process, by carrying neurotransmitter chemicals from the extracellular space into the cytoplasm of a...
s via phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
of the transporter protein, also known as a releasing agent
Releasing agent
A releasing agent , or simply releaser, is a drug that induces the release of a neurotransmitter from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitter. Many drugs use neurotransmitter release to exert their psychological and...
. Pure vesicular reuptake inhibitors tend to actually lower synaptic
Synaptic
Synaptic may refer to:*Synapse, part of the nervous system*Synapsis, the pairing of two homologous chromosomes*Synaptic , a Linux graphical package management program for APT See also...
neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...
s, as blocking
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
the repackaging
Active transport
Active transport is the movement of a substance against its concentration gradient . In all cells, this is usually concerned with accumulating high concentrations of molecules that the cell needs, such as ions, glucose, and amino acids. If the process uses chemical energy, such as from adenosine...
of, and storage
Synaptic vesicle
In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...
of the neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
in question leaves them vulnerable to degradation
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
via enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s such as monoamine oxidase
Monoamine oxidase
L-Monoamine oxidases are a family of enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. The enzyme was originally discovered by Mary Bernheim in the liver and was named tyramine oxidase...
(MAO) which exist in the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
. With vesicular transport
Active transport
Active transport is the movement of a substance against its concentration gradient . In all cells, this is usually concerned with accumulating high concentrations of molecules that the cell needs, such as ions, glucose, and amino acids. If the process uses chemical energy, such as from adenosine...
blocked
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
, neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
stores quickly become depleted.
Reserpine
Reserpine
Reserpine is an indole alkaloid antipsychotic and antihypertensive drug that has been used for the control of high blood pressure and for the relief of psychotic symptoms, although because of the development of better drugs for these purposes and because of its numerous side-effects, it is rarely...
(Serpasil) is an irreversible
Irreversibility
In science, a process that is not reversible is called irreversible. This concept arises most frequently in thermodynamics, as applied to processes....
and competitive
Competitive inhibition
Competitive inhibition is a form of enzyme inhibition where binding of the inhibitor to the active site on the enzyme prevents binding of the substrate and vice versa.-Mechanism:...
inhibitor of the vesicular monoamine transporter 2 (VMAT2), and is a classic example of a vesicular reuptake inhibitor.
Selective for one neurotransmitter
- Adenosine reuptake inhibitorAdenosine reuptake inhibitorAn adenosine reuptake inhibitor is a type of drug which acts as a reuptake inhibitor for the purine nucleoside and neurotransmitter adenosine by blocking the action of one or more of the equilibrative nucleoside transporters . This in turn leads to increased extracellular concentrations of...
(AdoRI)- DilazepDilazepDilazep is a vasodilator that acts as an adenosine reuptake inhibitor....
(Cormelian), dipyridamoleDipyridamoleDipyridamole is a drug that inhibits thrombus formation when given chronically and causes vasodilation when given at high doses over a short time.-Mechanism and effects:...
(Persantine), hexobendineHexobendineHexobendine is a vasodilator that acts as an adenosine reuptake inhibitor....
(Ustimon), pentoxifylline (Trental)
- Dilazep
- Dopamine reuptake inhibitorDopamine reuptake inhibitorA dopamine reuptake inhibitor is a type of drug that acts as a reuptake inhibitor for the neurotransmitter dopamine by blocking the action of the dopamine transporter...
(DRI)- Amfonelic acidAmfonelic acidAmfonelic acid is a psychoactive drug and research chemical used in scientific studies. It was discovered while researchers were investigating novel antibiotics. It acts as a potent and highly selective dopamine reuptake inhibitor . It has a moderately long half-life of approximately 12 hours...
(AFA; WIN 25,978), benocyclidineBenocyclidineBenocyclidine , or benzothiophenylcyclohexylpiperidine , is a psychoactive drug and research chemical of the arylcyclohexylamine and piperidine chemical classes. It acts a potent and selective dopamine reuptake inhibitor and a stimulant...
(BTCP; GK-13), troparil (β-CPT; WIN 35,065-2), vanoxerineVanoxerineVanoxerine is a piperazine derivative which is a potent and selective DRI. GBR-12909 binds to the target site on the DAT ~ 500 times more strongly than cocaine, but simultaneously inhibits the release of dopamine...
(GBR-12,909)
- Amfonelic acid
- Endocannabinoid reuptake inhibitorEndocannabinoid reuptake inhibitorEndocannabinoid reuptake inhibitors , similar to cannabinoid reuptake inhibitors , are substances which limit or completely stop the reabsorption of endocannabinoid neurotransmitters into their corresponding pre-synaptic neurones.-Etymology:...
(eCBRI)- AM-404, O-2093, OMDM-2, UCM-707, VDM-11VDM-11VDM-11 is a potent cannabinoid reuptake inhibitor. It is light-sensitive and therefore must be stored within an inert gas such as argon, in a dark place and at an ideal temperature of -20ºC. This gold-colored substance is rarely found outside research laboratories.-See also:* Endocannabinoid...
- AM-404, O-2093, OMDM-2, UCM-707, VDM-11
- Glutamate reuptake inhibitor (GluRI) or excitatory amino acid reuptake inhibitor (EAARI)
- Dihydrokainic acid, PDC, WAY-213,613WAY-213,613WAY-213,613 is a drug which acts as a reuptake inhibitor for the glutamate transporter subtype EAAT2, selective over other glutamate transporter subtypes and highly selective over metabotropic and ionotropic glutamate receptors. It is used in scientific research into the function of the glutamate...
- Dihydrokainic acid, PDC, WAY-213,613
- GABA reuptake inhibitorGABA reuptake inhibitorA GABA reuptake inhibitor is a type of drug which acts as a reuptake inhibitor for the neurotransmitter gamma-Aminobutyric acid by blocking the action of the gamma-Aminobutyric acid transporters...
(GRI)- DeramciclaneDeramciclaneDeramciclane is a drug which acts as an antagonist at the 5-HT2A receptor, as an inverse agonist at the 5-HT2C receptor, and as a GABA reuptake inhibitor....
(EGIS-3886), nipecotic acidNipecotic acidNipecotic acid is a GABA reuptake inhibitor used in scientific research....
, tiagabineTiagabineTiagabine -Indications:Tiagabine is approved by U.S. Food and Drug Administration as an adjunctive treatment for partial seizures in ages 12 and up. It may also be prescribed to treat anxiety disorders and neuropathic pain . For anxiety and neuropathic pain, tiagabine is used primarily to augment...
(Gabitril)
- Deramciclane
- Glycine reuptake inhibitor (GlyRI)
- ACPPB, ALX-5407, glycyldodecylamide, ORG-24,589, sarcosineSarcosineSarcosine, also known as N-methylglycine, is an intermediate and byproduct in glycine synthesis and degradation. Sarcosine is metabolized to glycine by the enzyme sarcosine dehydrogenase, while glycine-N-methyl transferase generates sarcosine from glycine. Sarcosine is a natural amino acid found in...
, SSR-103,800, SSR-504,734
- ACPPB, ALX-5407, glycyldodecylamide, ORG-24,589, sarcosine
- Norepinephrine reuptake inhibitorNorepinephrine reuptake inhibitorA norepinephrine reuptake inhibitor or adrenergic reuptake inhibitor , is a type of drug which acts as a reuptake inhibitor for the neurotransmitters norepinephrine and epinephrine by blocking the action of the norepinephrine transporter...
(NRI) or Adrenergic reuptake inhibitor (ARI))- Atomoxetine (Strattera), nisoxetineNisoxetineNisoxetine is a drug which inhibits the reuptake of norepinephrine . It is a racemic compound with two isomers...
(LY-94,939), reboxetineReboxetineReboxetine is a drug marketed as an antidepressant for use in the treatment of clinical depression, panic disorder and ADD/ADHD, developed by Pharmacia . Its mesylate salt is sold under tradenames including Edronax, Norebox, Prolift, Solvex, Davedax or Vestra...
(Edronax, Vestra), viloxazineViloxazineViloxazine is a bicyclic antidepressant morpholine derivative that acts as a selective norepinephrine reuptake inhibitor...
(Vivalan)
- Atomoxetine (Strattera), nisoxetine
- Serotonin reuptake inhibitor (SRI)
- EscitalopramEscitalopramEscitalopram is an antidepressant of the selective serotonin reuptake inhibitor class. It is approved by the U.S...
(Lexapro, Cipralex), fluoxetineFluoxetineFluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...
(Prozac), sertralineSertralineSertraline hydrochloride is an antidepressant of the selective serotonin reuptake inhibitor class. It was introduced to the market by Pfizer in 1991. Sertraline is primarily used to treat major depression in adult outpatients as well as obsessive–compulsive, panic, and social anxiety disorders in...
(Zoloft, Lustral)
- Escitalopram
Selective for several neurotransmitters
- Serotonin-norepinephrine reuptake inhibitorSerotonin-norepinephrine reuptake inhibitorSerotonin–norepinephrine reuptake inhibitors are a class of antidepressant drugs used in the treatment of major depression and other mood disorders...
(SNRI)- DesvenlafaxineDesvenlafaxineDesvenlafaxine , also known as O-desmethylvenlafaxine, is an antidepressant of the serotonin-norepinephrine reuptake inhibitor class developed and marketed by Wyeth . Desvenlafaxine is a synthetic form of the major active metabolite of venlafaxine...
(Pristiq), duloxetineDuloxetineDuloxetine is a serotonin-norepinephrine reuptake inhibitor manufactured and marketed by Eli Lilly. It is effective for major depressive disorder and has been shown to be as effective as venlafaxine for generalized anxiety disorder...
(Cymbalta), milnacipranMilnacipranMilnacipran is a serotonin–norepinephrine reuptake inhibitor used in the clinical treatment of fibromyalgia...
(Dalcipran, Ixel, Savella), venlafaxineVenlafaxineVenlafaxine is an antidepressant of the serotonin-norepinephrine reuptake inhibitor class. First introduced by Wyeth in 1993, now marketed by Pfizer, it is licensed for the treatment of major depressive disorder , as a treatment for generalized anxiety disorder, and comorbid indications in...
(Effexor)
- Desvenlafaxine
- Norepinephrine-dopamine reuptake inhibitorNorepinephrine-dopamine reuptake inhibitorA norepinephrine-dopamine reuptake inhibitor is a drug which acts as a reuptake inhibitor for the neurotransmitters norepinephrine and dopamine by blocking the action of the norepinephrine transporter and the dopamine transporter , respectively...
(NDRI)- AmineptineAmineptineAmineptine was developed by the French Society of Medical research in the 1960s. Under the trade-names is used as an atypical tricyclic antidepressant that selectively inhibits the reuptake of dopamine and to a lesser extent norepinephrine, thus exerting a powerful and fast-acting...
(Survector), bupropionBupropionBupropion is an atypical antidepressant and smoking cessation aid. The drug is a non-tricyclic antidepressant and differs from most commonly prescribed antidepressants such as SSRIs, as its primary pharmacological action is thought to be norepinephrine-dopamine reuptake inhibition...
(Wellbutrin, Zyban), methylenedioxypyrovalerone, methylphenidateMethylphenidateMethylphenidate 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...
(Ritalin, Concerta), pipradrolPipradrolPipradrol is a mild central nervous system stimulant that is no longer widely used in most countries due to concerns about its abuse potential, although this is less of a problem than with other stimulants that still are in current use such as methylphenidate...
(Meretran)
- Amineptine
- Serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI)
- CocaineCocaineCocaine 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...
, indatralineIndatralineIndatraline is a non-selective monoamine transporter inhibitor that has been shown to block the reuptake of dopamine, norepinephrine, and serotonin with effects similar to those of cocaine...
(Lu-19-005), nefopamNefopamNefopam is a centrally-acting but non-opioid analgesic drug of the benzoxazocine chemical class which was developed by Riker Laboratories in the 1960s. It is widely used, mainly in European countries, for the relief of moderate to severe pain as an alternative to opioid analgesic drugs...
(Acupan), tesofensineTesofensineTesofensine is a serotonin–noradrenaline–dopamine reuptake inhibitor from the phenyltropane family of drugs, which is being developed for the treatment of obesity...
(NS-2330)
- Cocaine
- Serotonin-norepinephrine-dopamine-GABA-glutamate reuptake inhibitor
- AdhyperforinAdhyperforinAdhyperforin is a phytochemical found in the members of the plant genus Hypericum including St. John's Wort. It has a very similar pharmacological profile to hyperforin and acts as a TRPC6 ion channel activator, thereby inhibiting the reuptake of various neurotransmitters including serotonin,...
, hyperforinHyperforinHyperforin is a phytochemical produced by some of the members of the plant genus Hypericum, notably Hypericum perforatum .- Occurrence :...
- Adhyperforin