Neuropharmacology
Encyclopedia
Neuropharmacology is the study of how drugs affect cellular function in the nervous system. There are two main branches of neuropharmacology: behavioral and molecular. Behavioral neuropharmacology focuses on the study of how drugs affect human behavior (neuropsychopharmacology
), including the study of how drug dependence and addiction
affect the human brain
. Molecular neuropharmacology involves the study of neurons and their neurochemical
interactions, with the overall goal of developing drugs that have beneficial effects on neurological function. Both of these fields are closely connected, since both are concerned with the interactions of neurotransmitters, neuropeptides, neurohormones, neuromodulators, enzymes, second messengers, co-transporters, ion channels, and receptor proteins in the central
and peripheral nervous system
s. Studying these interactions, researchers are developing drugs to treat many different neurological disorders, including pain
, neurodegenerative diseases such as Parkinson's disease
and Alzheimer's disease
, psychological disorders, addiction, and many others.
out a basic understanding of the nervous system and how nerves communicate between one another. Before this discovery, there were drugs, however, that had been found that demonstrated some type of influence on the nervous system. In the 1930’s, French scientists began working with a compound called phenothiazine in the hope of synthesizing a drug that would be able to combat malaria. Though this drug showed very little hope in the use against malaria infected individuals, it was found to have sedative effects along with what appeared to be beneficial effects toward patients with Parkinson’s disease. This black box method, where an investigator would administer a drug and examine the response without knowing how to relate drug action to patient response, was the main approach to this field, until, in the late 1940s and early 1950s, scientists were able to identify specific neurotransmitters, such as norepinephrine
(involved in the constriction of blood vessels and the increase in heart rate and blood pressure), dopamine
(the chemical whose shortage is involved in Parkinson’s disease), and serotonin
(soon to be recognized as deeply connected to depression). In the 1950s, scientists also became better able to measure levels of specific neurochemicals in the body and thus correlate these levels with behavior. The invention of the voltage clamp
in 1949 allowed for the study of ion channels and the nerve action potential
. These two major historical events in neuropharmacology allowed scientists not only to study how information is transferred from one neuron to another, but also how a neuron processes this information within itself.
Neurons are known as excitable cells because on its surface membrane there are an abundance of proteins known as ion-channels that allow small charged particles to pass in and out of the cell. The structure of the neuron allows chemical information to be received by its dendrites, propagated through the perikaryon (cell body) and down its axon
, and eventually passing on to other neurons through its axon terminal
.
These voltage-gated ion channels allow for rapid depolarization
throughout the cell. This depolarization, if it reaches a certain threshold, will cause an action potential
. Once the action potential reaches the axon terminal, it will cause an influx of calcium ions into the cell. The calcium ions will then cause vesicles, small packets filled with neurotransmitters, to bind to the cell membrane and release its contents into the synapse. This cell is known as the pre-synaptic neuron, and the cell that interacts with the neurotransmitters released is known as the post-synaptic neuron. Once the neurotransmitter is released into the synapse, it can either bind to receptors on the post-synaptic cell, the pre-synaptic cell can re-uptake it and save it for later transmission, or it can be broken down by enzymes in the synapse specific to that certain neurotransmitter. These three different actions are major areas where drug action can effect communication between neurons.
There are two types of receptors that neurotransmitters interact with on a post-synaptic neuron. The first types of receptors are ligand-gated ion channels or LGIC’s. LGIC receptors are the fastest types of transduction from chemical signal to electrical signal. Once the neurotransmitter binds to the receptor it will cause a conformational change that will allow ions to directly flow into the cell. The second types are known as G-protein-coupled receptors or GPCR’s. These are much slower than LGIC’s due to an increase in the amount of biochemical reactions that must take place intracellularly. Once the neurotransmitter binds to the GPCR protein it causes a cascade of intracellular interactions that can lead to many different types of changes in cellular biochemistry, physiology, and gene expression. Neurotransmitter/receptor interactions in the field of neuropharmacology are extremely important because many drugs that are developed today have to do with disrupting this binding process.
). There are a few technical words that must be defined when relating neurotransmission to receptor action:
The following neurotransmitter/receptor interactions can be affected by synthetic compounds that act as one of the three above. Sodium/potassium ion channels can also be manipulated throughout a neuron to induce inhibitory effects of action potentials.
This GABAA receptor contains many binding sites that allow conformational changes and are the primary target for drug development. The most common of these binding sites, benzodiazepine, allows for both agonist and antagonist effects on the receptor. A common drug, diazepam
, acts as an allosteric enhancer at this binding site. Another receptor for GABA, known as GABAB, can be enhanced by a molecule called baclofen. This molecule acts as an agonist, therefore activating the receptor, and is known to help control and decrease spastic movement.
neurotransmitter mediates synaptic transmission by binding to five specific GPCR's. These five receptor proteins are separated into two classes due to whether the response elicits a excitatory or inhibitory response on the post-synaptic cell. There are many types of drugs, legal and illegal, that effect dopamine and its interactions in the brain. With Parkinson's disease, a disease that decreases the amount of dopamine in the brain, the dopamine precursor Levodopa is given to the patient due to the fact that dopamine cannot cross the blood-brain barrier
and L-dopa can. Some dopamine agonists are also given to Parkinson's patients that have a disorder known as restless leg syndrome or RLS. Some examples of these are ropinirole
and pramipexole
.
Psychological disorders like that of attention deficit hyperactivity disorder (ADHD) can be treated with drugs like methylphenidate
(also known as Ritalin) which block the re-uptake of dopamine by the pre-synaptic cell, thereby providing an increase of dopamine left in the synaptic gap. This increase in synaptic dopamine will increase binding to receptors of the post-synaptic cell. This same process is also used by other illegal stimulant drugs such as cocaine
.
neurotransmitter has the ability to mediate synaptic transmission through either GPCR's or LGIC receptors. Depending on what part of the brain region serotonin is being acted upon, will depend on whether the output is either increasing or decreasing post-synaptic responses. The most popular and widely used drugs in the regulation of serotonin during depression are known as SSRI's or selective serotonin reuptake inhibitors. These drugs inhibit the transport of serotonin back into the pre-synaptic neuron, leaving more serotonin in the synaptic gap to be used.
Before the discovery of SSRI's, there were also very many drugs that inhibited the enzyme that broke down serotonin. MAOI's or monoamine oxidase inhibitors increased the amount of serotonin in the pre-synaptic cell, but had many side effects including intense migraines and high blood pressure. This was eventually linked to the drug interacting with a common chemical known as tyramine
found in many types of food.
is a neuroprotective drug that blocks sodium ion channels. Since these channels can not activate, there is no action potential and the neuron does not perform any transduction of chemical signals into electrical signals and the signal does not move on. This drug is used as an anesthetic along with sedative properties.
for human behavior and drug development) Most research has shown that the major part of the brain that reinforces addiction through neurochemical reward is the nucleus accumbens
. The image to the right shows how dopamine and serotonin are projected into this area. Chronic alcohol abuse can cause major dependence and addiction. How this addiction occurs is described below.
causing many of the neurons in the brain to become hyper-excitable during withdrawal from alcohol. Since GABA, for the most part, is an inhibitory neurotransmitter, a decrease in its amount will result in a feeling of anxiety. Along with GABA, there have been many links to other neurotransmitters that are affected by long-term use of alcohol, including dopamine
, serotonin
, and glutamate.
is a neurodegenerative disease described by the selective loss of dopaminergic
neurons located in the substantia nigra
. Today, the most commonly used drug to combat this disease is levodopa or L-DOPA. This precursor to dopamine can penetrate through the blood-brain barrier
whereas the neurotransmitter dopamine cannot. There has been extensive research to determine whether L-dopa is a better treatment for Parkinson's disease rather than other dopamine agonists. Some believe that the long term use of L-dopa will compromise neuroprotection and thus eventually lead to dopaminergic cell death. Though there has been no proof, in-vivo or in-vitro, some still believe that the better long-term use of dopamine agonists be better for the patient.
, the knowledge of this disease is far from complete to explain, making it difficult to develop methods for treatment. In the brain of Alzheimer's patients, both neuronal nicotinic acetylcholine (nACh) receptors and NMDA receptors are known to be down-regulated. Thus four anticholinesterases have been developed and approved by the U.S. Food and Drug Administration (FDA) for the treatment in the U.S.A. However, these are not ideal drugs considering their side effects and limited effectiveness. One promising drug, nefiracetam
, is being developed for the treatment of Alzheimer's and other patients with dementia, and has unique actions in potentiating the activity of both nACh receptors and NMDA receptors.
or SARs is a major area of research within neuropharmacology which tries to modify the effect or the potency (i.e., activity) of bioactive chemical compounds by modifying their chemical structure.
Neuropsychopharmacology
Neuropsychopharmacology is an interdisciplinary science related to psychopharmacology and fundamental neuroscience...
), including the study of how drug dependence and addiction
Substance dependence
The section about substance dependence in the Diagnostic and Statistical Manual of Mental Disorders does not use the word addiction at all. It explains:...
affect the human brain
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...
. Molecular neuropharmacology involves the study of neurons and their neurochemical
Neurochemistry
Neurochemistry is the specific study of neurochemicals, which include neurotransmitters and other molecules such as neuro-active drugs that influence neuron function. This principle closely examines the manner in which these neurochemicals influence the network of neural operation...
interactions, with the overall goal of developing drugs that have beneficial effects on neurological function. Both of these fields are closely connected, since both are concerned with the interactions of neurotransmitters, neuropeptides, neurohormones, neuromodulators, enzymes, second messengers, co-transporters, ion channels, and receptor proteins in the central
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
and peripheral nervous system
Peripheral nervous system
The peripheral nervous system consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain...
s. Studying these interactions, researchers are developing drugs to treat many different neurological disorders, including pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
, neurodegenerative diseases such as Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
and Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
, psychological disorders, addiction, and many others.
History
Neuropharmacology did not appear in the scientific field until, in the early part of the 20th century, scientists were able to figureout a basic understanding of the nervous system and how nerves communicate between one another. Before this discovery, there were drugs, however, that had been found that demonstrated some type of influence on the nervous system. In the 1930’s, French scientists began working with a compound called phenothiazine in the hope of synthesizing a drug that would be able to combat malaria. Though this drug showed very little hope in the use against malaria infected individuals, it was found to have sedative effects along with what appeared to be beneficial effects toward patients with Parkinson’s disease. This black box method, where an investigator would administer a drug and examine the response without knowing how to relate drug action to patient response, was the main approach to this field, until, in the late 1940s and early 1950s, scientists were able to identify specific neurotransmitters, such as norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
(involved in the constriction of blood vessels and the increase in heart rate and blood pressure), 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...
(the chemical whose shortage is involved in Parkinson’s disease), and 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...
(soon to be recognized as deeply connected to depression). In the 1950s, scientists also became better able to measure levels of specific neurochemicals in the body and thus correlate these levels with behavior. The invention of the voltage clamp
Voltage clamp
The voltage clamp is used by electrophysiologists to measure the ion currents across the membrane of excitable cells, such as neurons, while holding the membrane voltage at a set level. Cell membranes of excitable cells contain many different kinds of ion channels, some of which are voltage gated...
in 1949 allowed for the study of ion channels and the nerve action potential
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...
. These two major historical events in neuropharmacology allowed scientists not only to study how information is transferred from one neuron to another, but also how a neuron processes this information within itself.
Overview
Neuropharmacology is a very broad region of science that encompasses many aspects of the nervous system from single neuron manipulation to entire areas of the brain, spinal cord, and peripheral nerves. To better understand the basis behind drug development, one must first understand how neurons communicate between one another. This article will focus on both behavioral and molecular neuropharmacology; the major receptors, ion channels, and neurotransmitters manipulated through drug action and how people with a neurological disorder benefit from this drug action.Neurochemical interactions
To understand the potential advances in medicine that neuropharmacology can bring, it is important to understand how human behavior and thought processes are transferred from neuron to neuron and how medications can alter the chemical foundations of these processes.Neurons are known as excitable cells because on its surface membrane there are an abundance of proteins known as ion-channels that allow small charged particles to pass in and out of the cell. The structure of the neuron allows chemical information to be received by its dendrites, propagated through the perikaryon (cell body) and down its axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
, and eventually passing on to other neurons through its axon terminal
Axon terminal
Axon terminals are distal terminations of the branches of an axon. An axon nerve fiber is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body, or soma, in order to transmit those impulses to other neurons.Neurons are...
.
Depolarization
In biology, depolarization is a change in a cell's membrane potential, making it more positive, or less negative. In neurons and some other cells, a large enough depolarization may result in an action potential...
throughout the cell. This depolarization, if it reaches a certain threshold, will cause an action potential
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...
. Once the action potential reaches the axon terminal, it will cause an influx of calcium ions into the cell. The calcium ions will then cause vesicles, small packets filled with neurotransmitters, to bind to the cell membrane and release its contents into the synapse. This cell is known as the pre-synaptic neuron, and the cell that interacts with the neurotransmitters released is known as the post-synaptic neuron. Once the neurotransmitter is released into the synapse, it can either bind to receptors on the post-synaptic cell, the pre-synaptic cell can re-uptake it and save it for later transmission, or it can be broken down by enzymes in the synapse specific to that certain neurotransmitter. These three different actions are major areas where drug action can effect communication between neurons.
There are two types of receptors that neurotransmitters interact with on a post-synaptic neuron. The first types of receptors are ligand-gated ion channels or LGIC’s. LGIC receptors are the fastest types of transduction from chemical signal to electrical signal. Once the neurotransmitter binds to the receptor it will cause a conformational change that will allow ions to directly flow into the cell. The second types are known as G-protein-coupled receptors or GPCR’s. These are much slower than LGIC’s due to an increase in the amount of biochemical reactions that must take place intracellularly. Once the neurotransmitter binds to the GPCR protein it causes a cascade of intracellular interactions that can lead to many different types of changes in cellular biochemistry, physiology, and gene expression. Neurotransmitter/receptor interactions in the field of neuropharmacology are extremely important because many drugs that are developed today have to do with disrupting this binding process.
Molecular neuropharmacology
Molecular neuropharmacology involves the study of neurons and their neurochemical interactions, and receptors on neurons, with the goal of developing new drugs that will treat neurological disorders such as pain, neurodegenerative diseases, and psychological disorders (also known in this case as neuropsychopharmacologyNeuropsychopharmacology
Neuropsychopharmacology is an interdisciplinary science related to psychopharmacology and fundamental neuroscience...
). There are a few technical words that must be defined when relating neurotransmission to receptor action:
- Agonist—this is when a molecule binds to a receptor protein and activates that receptor
- Competitive antagonist—this is when a molecule binds to the same site on the receptor protein as the agonist, preventing activation of the receptor.
- Non-competitive antagonist—this is when a molecule binds to a receptor protein on a different site than that of the agonist, but causes a conformational change in the protein that does not allow activation.
The following neurotransmitter/receptor interactions can be affected by synthetic compounds that act as one of the three above. Sodium/potassium ion channels can also be manipulated throughout a neuron to induce inhibitory effects of action potentials.
GABA
The GABA neurotransmitter mediates the fast synaptic inhibition in the central nervous system. When GABA is released from its pre-synaptic cell it will bind to a receptor (most likely the GABAA receptor) that causes the post-synaptic cell to hyperpolarize (stay below its action potential threshold). This will counteract the effect of any excitatory manipulation from other neurotransmitter/receptor interactions.This GABAA receptor contains many binding sites that allow conformational changes and are the primary target for drug development. The most common of these binding sites, benzodiazepine, allows for both agonist and antagonist effects on the receptor. A common drug, diazepam
Diazepam
Diazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...
, acts as an allosteric enhancer at this binding site. Another receptor for GABA, known as GABAB, can be enhanced by a molecule called baclofen. This molecule acts as an agonist, therefore activating the receptor, and is known to help control and decrease spastic movement.
Dopamine
The dopamineDopamine
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...
neurotransmitter mediates synaptic transmission by binding to five specific GPCR's. These five receptor proteins are separated into two classes due to whether the response elicits a excitatory or inhibitory response on the post-synaptic cell. There are many types of drugs, legal and illegal, that effect dopamine and its interactions in the brain. With Parkinson's disease, a disease that decreases the amount of dopamine in the brain, the dopamine precursor Levodopa is given to the patient due to the fact that dopamine cannot cross the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
and L-dopa can. Some dopamine agonists are also given to Parkinson's patients that have a disorder known as restless leg syndrome or RLS. Some examples of these are ropinirole
Ropinirole
Ropinirole is a non-ergoline dopamine agonist. It is manufactured by GlaxoSmithKline , Cipla and Sun Pharmaceutical. It is used in the treatment of Parkinson's disease...
and pramipexole
Pramipexole
Pramipexole is a non-ergoline dopamine agonist indicated for treating early-stage Parkinson's disease and restless legs syndrome...
.
Psychological disorders like that of attention deficit hyperactivity disorder (ADHD) can be treated with drugs like methylphenidate
Methylphenidate
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...
(also known as Ritalin) which block the re-uptake of dopamine by the pre-synaptic cell, thereby providing an increase of dopamine left in the synaptic gap. This increase in synaptic dopamine will increase binding to receptors of the post-synaptic cell. This same process is also used by other illegal stimulant drugs 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...
.
Serotonin
The serotoninSerotonin
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...
neurotransmitter has the ability to mediate synaptic transmission through either GPCR's or LGIC receptors. Depending on what part of the brain region serotonin is being acted upon, will depend on whether the output is either increasing or decreasing post-synaptic responses. The most popular and widely used drugs in the regulation of serotonin during depression are known as SSRI's or selective serotonin reuptake inhibitors. These drugs inhibit the transport of serotonin back into the pre-synaptic neuron, leaving more serotonin in the synaptic gap to be used.
Before the discovery of SSRI's, there were also very many drugs that inhibited the enzyme that broke down serotonin. MAOI's or monoamine oxidase inhibitors increased the amount of serotonin in the pre-synaptic cell, but had many side effects including intense migraines and high blood pressure. This was eventually linked to the drug interacting with a common chemical known as tyramine
Tyramine
Tyramine is a naturally occurring monoamine compound and trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent...
found in many types of food.
Ion channels
Ion channels located on the surface membrane of the neuron, allows for an influx of sodium ions and outward movement of potassium ions during an action potential. Selectively blocking these ion channels will decrease the likelihood of an action potential to occur. The drug riluzoleRiluzole
Riluzole is a drug used to treat amyotrophic lateral sclerosis. It delays the onset of ventilator-dependence or tracheostomy in selected patients and may increase survival by approximately 3–5 months....
is a neuroprotective drug that blocks sodium ion channels. Since these channels can not activate, there is no action potential and the neuron does not perform any transduction of chemical signals into electrical signals and the signal does not move on. This drug is used as an anesthetic along with sedative properties.
Behavioral neuropharmacology
One form of behavioral neuropharmacology focuses on the study of drug dependence and how drug addiction affects the human mind. (see neuropsychopharmacologyNeuropsychopharmacology
Neuropsychopharmacology is an interdisciplinary science related to psychopharmacology and fundamental neuroscience...
for human behavior and drug development) Most research has shown that the major part of the brain that reinforces addiction through neurochemical reward is 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...
. The image to the right shows how dopamine and serotonin are projected into this area. Chronic alcohol abuse can cause major dependence and addiction. How this addiction occurs is described below.
Alcoholism
The behavior effects of alcohol are primarily produced through its actions on the brain. Intoxication is a short-term result of alcohol present in the brain that is attributed to changes in neuronal communication. Tolerance and dependence are more long-term results that involve molecular and cellular changes due to increased exposure to alcohol. Researchers have found many areas in neuronal function that alter due to chronic alcohol exposure. In the GABAergic system, the GABAA receptor is modified effecting the efficiency and timing of inhibitory synaptic transmission. This is also usually accompanied by an increase or decrease in the release of the neurotransmitter GABAGabâ
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...
causing many of the neurons in the brain to become hyper-excitable during withdrawal from alcohol. Since GABA, for the most part, is an inhibitory neurotransmitter, a decrease in its amount will result in a feeling of anxiety. Along with GABA, there have been many links to other neurotransmitters that are affected by long-term use of alcohol, including 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...
, 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...
, and glutamate.
Parkinson's disease
Parkinson's diseaseParkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
is a neurodegenerative disease described by the selective loss of dopaminergic
Dopaminergic
Dopaminergic means related to the neurotransmitter dopamine. For example, certain proteins such as the dopamine transporter , vesicular monoamine transporter 2 , and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine...
neurons located in the substantia nigra
Substantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
. Today, the most commonly used drug to combat this disease is levodopa or L-DOPA. This precursor to dopamine can penetrate through the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
whereas the neurotransmitter dopamine cannot. There has been extensive research to determine whether L-dopa is a better treatment for Parkinson's disease rather than other dopamine agonists. Some believe that the long term use of L-dopa will compromise neuroprotection and thus eventually lead to dopaminergic cell death. Though there has been no proof, in-vivo or in-vitro, some still believe that the better long-term use of dopamine agonists be better for the patient.
Alzheimer's disease
While there are a variety of hypotheses that have been proposed for the cause of Alzheimer's diseaseAlzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
, the knowledge of this disease is far from complete to explain, making it difficult to develop methods for treatment. In the brain of Alzheimer's patients, both neuronal nicotinic acetylcholine (nACh) receptors and NMDA receptors are known to be down-regulated. Thus four anticholinesterases have been developed and approved by the U.S. Food and Drug Administration (FDA) for the treatment in the U.S.A. However, these are not ideal drugs considering their side effects and limited effectiveness. One promising drug, nefiracetam
Nefiracetam
Nefiracetam is a nootropic antidementia drug of the racetam family.Nefiracetam's cytoprotective actions are mediated by enhancement of GABAergic, cholinergic, and monoaminergic neuronal systems that give antiamnesia effects to the Alzheimer's type and cerebrovascular type of dementia.Nefiracetam...
, is being developed for the treatment of Alzheimer's and other patients with dementia, and has unique actions in potentiating the activity of both nACh receptors and NMDA receptors.
Future
With an increase in technology and our understanding of the nervous system, the development of drugs will continue to rise with an increase in drug sensitivity and specificity. Structure-activity relationshipStructure-activity relationship
The structure–activity relationship is the relationship between the chemical or 3D structure of a molecule and its biological activity. The analysis of SAR enables the determination of the chemical groups responsible for evoking a target biological effect in the organism...
or SARs is a major area of research within neuropharmacology which tries to modify the effect or the potency (i.e., activity) of bioactive chemical compounds by modifying their chemical structure.
See also
- NeuropsychopharmacologyNeuropsychopharmacologyNeuropsychopharmacology is an interdisciplinary science related to psychopharmacology and fundamental neuroscience...
- Structure-activity relationshipStructure-activity relationshipThe structure–activity relationship is the relationship between the chemical or 3D structure of a molecule and its biological activity. The analysis of SAR enables the determination of the chemical groups responsible for evoking a target biological effect in the organism...
- NeurotechnologyNeurotechnologyNeurotechnology is any technology that has a fundamental influence on how people understand the brain and various aspects of consciousness, thought, and higher order activities in the brain...
- NeurotransmissionNeurotransmissionNeurotransmission , 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...
- ElectrophysiologyElectrophysiologyElectrophysiology is the study of the electrical properties of biological cells and tissues. It involves measurements of voltage change or electric current on a wide variety of scales from single ion channel proteins to whole organs like the heart...