Monoamine transporters are structures in nerve-cell
membraneThe cell membrane is the biological membrane separating the interior of a cell from the outside environment....
s that function as
neurotransmitter transporterNeurotransmitter transporters are a class of membrane transport proteins that span cellular membranes and that serve to carry neurotransmitters across these membranes and to transport them to specific locations. There are more than twenty types of neurotransmitter transporters...
s transferring
monoamine neurotransmitterMonoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group that is connected to an aromatic ring by a two-carbon chain...
s in or out of
cellThe cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of an organism that is classified as living, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos...
s.
There are several different monoamine transporters:
- The dopamine
Dopamine is a neurotransmitter occurring in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this phenethylamine functions as a neurotransmitter, activating the five types of dopamine receptors — D
1, D
2, D
3, D
4, and...
transporter, DATThe dopamine transporter is a membrane-spanning protein that binds the neurotransmitter dopamine; DAT provides the primary mechanism through which dopamine is cleared from synapses, transporting dopamine from the synapse into a neuron...
.
- The norepinephrine
Noradrenaline or norepinephrine is a catecholamine with dual roles as a hormone and a neurotransmitter....
transporter, NETThe norepinephrine transporter or NET is a monoamine transporter that transports the neurotransmitter norepinephrine from the synapse back to its vesicles for storage until later use. It also appears to transport the neurotransmitter dopamine in the same way, but to a lesser degree...
.
- The serotonin
Serotonin is a monoamine neurotransmitter. It is found extensively in the gastrointestinal tract of animals, and about 80 to 90 percent of the human body's total serotonin is located in the enterochromaffin cells in the gut, where it is used to regulate intestinal movements...
transporter, SERTThe 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...
.
- The less-specific monoamine transporter, PMAT
The plasma membrane monoamine transporter is a low-affinity monoamine transporter protein.This protein is an integral membrane protein that transports the monoamine neurotransmitters as well as adenosine, from synaptic spaces into presynaptic neurons or neighboring glial cells...
.
DAT, NET and SERT are related to each other, and each consists of a structure of 12
transmembrane helicesTransmembrane domain usually denotes a single transmembrane alpha helix of a transmembrane protein. It is called a "domain" because an alpha-helix in a membrane can be folded independently from the rest of the protein, similar to domains of water-soluble proteins...
.
Many drugs, such as
antidepressantAn antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia. Drugs including the monoamine oxidase inhibitors , tricyclic antidepressants , tetracyclic antidepressants , selective serotonin reuptake inhibitors , and serotonin-norepinephrine...
s and psychoactives affect the monoamine transporters (MATs).
Modern antidepressants typically work by enhancing serotonergic, noradrenergic or dopaminergic
neurotransmissionNeurotransmission , also called synaptic transmission, is an electrical movement within synapses caused by a propagation of nerve impulses...
by binding to the corresponding transporter, and thereby inhibiting neurotransmitter
reuptakeReuptake, 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....
and raising active levels in the synapse.
Monoamine transporters are structures in nerve-cell
membraneThe cell membrane is the biological membrane separating the interior of a cell from the outside environment....
s that function as
neurotransmitter transporterNeurotransmitter transporters are a class of membrane transport proteins that span cellular membranes and that serve to carry neurotransmitters across these membranes and to transport them to specific locations. There are more than twenty types of neurotransmitter transporters...
s transferring
monoamine neurotransmitterMonoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group that is connected to an aromatic ring by a two-carbon chain...
s in or out of
cellThe cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of an organism that is classified as living, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos...
s.
Types
There are several different monoamine transporters:
- The dopamine
Dopamine is a neurotransmitter occurring in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this phenethylamine functions as a neurotransmitter, activating the five types of dopamine receptors — D
1, D
2, D
3, D
4, and...
transporter, DATThe dopamine transporter is a membrane-spanning protein that binds the neurotransmitter dopamine; DAT provides the primary mechanism through which dopamine is cleared from synapses, transporting dopamine from the synapse into a neuron...
.
- The norepinephrine
Noradrenaline or norepinephrine is a catecholamine with dual roles as a hormone and a neurotransmitter....
transporter, NETThe norepinephrine transporter or NET is a monoamine transporter that transports the neurotransmitter norepinephrine from the synapse back to its vesicles for storage until later use. It also appears to transport the neurotransmitter dopamine in the same way, but to a lesser degree...
.
- The serotonin
Serotonin is a monoamine neurotransmitter. It is found extensively in the gastrointestinal tract of animals, and about 80 to 90 percent of the human body's total serotonin is located in the enterochromaffin cells in the gut, where it is used to regulate intestinal movements...
transporter, SERTThe 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...
.
- The less-specific monoamine transporter, PMAT
The plasma membrane monoamine transporter is a low-affinity monoamine transporter protein.This protein is an integral membrane protein that transports the monoamine neurotransmitters as well as adenosine, from synaptic spaces into presynaptic neurons or neighboring glial cells...
.
DAT, NET and SERT are related to each other, and each consists of a structure of 12
transmembrane helicesTransmembrane domain usually denotes a single transmembrane alpha helix of a transmembrane protein. It is called a "domain" because an alpha-helix in a membrane can be folded independently from the rest of the protein, similar to domains of water-soluble proteins...
.
Pharmacology
Many drugs, such as
antidepressantAn antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia. Drugs including the monoamine oxidase inhibitors , tricyclic antidepressants , tetracyclic antidepressants , selective serotonin reuptake inhibitors , and serotonin-norepinephrine...
s and psychoactives affect the monoamine transporters (MATs).
Modern antidepressants typically work by enhancing serotonergic, noradrenergic or dopaminergic
neurotransmissionNeurotransmission , also called synaptic transmission, is an electrical movement within synapses caused by a propagation of nerve impulses...
by binding to the corresponding transporter, and thereby inhibiting neurotransmitter
reuptakeReuptake, 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....
and raising active levels in the synapse. Examples include
fluoxetineFluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. Fluoxetine is approved for the treatment of major depression , obsessive-compulsive disorder , bulimia nervosa, anorexia nervosa, panic disorder and premenstrual dysphoric disorder...
, a
selective serotonin reuptake inhibitor Selective serotonin reuptake 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...
;
reboxetineReboxetine is an antidepressant drug used in the treatment of clinical depression, panic disorder and ADD/ADHD, developed by Pharmacia...
, a norepinephrine reuptake inhibitor and
bupropionBupropion is an atypical antidepressant that acts as a norepinephrine and dopamine reuptake inhibitor, and nicotinic antagonist...
, which inhibits both the norepinephrine and dopamine transporter.
The
euphoricEuphoria is medically recognized as a mental/emotional state defined as a sense of great elation and wellbeing. Technically, euphoria is an affect, but the term is often colloquially used to define emotion as an intense state of transcendent happiness combined with an overwhelming sense of wellbeing...
and
addictiveDrug addiction is a pathological condition which arises due to frequent drug use. The disorder of addiction involves the progression of acute drug use to the development of drug-seeking behavior, the vulnerability to relapse, and the decreased, slowed ability to respond to naturally rewarding stimuli...
properties of
amphetamineAmphetamine is a psychostimulant drug that is known to produce increased wakefulness and focus in association with decreased fatigue and appetite. Amphetamine is related to drugs such as methamphetamine and dextroamphetamine, which are a group of potent drugs that act by increasing levels of...
,
methamphetamineMethamphetamine also known as metamfetamine , dextromethamphetamine, methylamphetamine, N-methylamphetamine, and desoxyephedrine) is a psychostimulant and sympathomimetic drug. Methamphetamine enters the brain and triggers a cascading release of dopamine, serotonin and norepinephrine...
and
cocaineCocaine 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 and an appetite suppressant...
are thought to come from their potent DAT-blocking activity.
Triple MAT agents (aka SNDRI's oder TRI)
- PRC200-SS
- JNJ-7925476
JNJ-7925476 is a TRI antidepressant currently under development by Johnson & Johnson.These molecules were first prepared by Maryanoff, et al. during the late 1970's – 1980's...
- (+)-trans-5c
- nocaine-modafinil hybrids such as 16e.
- tropanes with "remote phenyl binding"