NEUROTRANSMITTERS-CLASSIFICATION,

RELEVANCE IN THE ETIOLOGY AND TREATMENT OF

MENTAL ILLNESS

INTRODUCTION

Neurotransmitters play an important role in the normal functioning of the

nervous system.many neurological diseases and all medications that act on
the nervous system influence the neurotransmitter system in some way.
Neurotransmitters transfer neuronal impulses to other information pathways
which lead to information flow and behaviour.
DEFINITION
Neurotransmitters are central nervous system biochemical involved in
facilitating the transmission of impulses across synapses between neurons.
Chemical neurotransmission is the process involving the release of
neurotransmitters by one neuron and binding the neurotransmitter molecule
to a receptor on another neuron.this process is affected by most drugs used
in psychiatry.
CRITERIA OF A NEUROTRANSMITTER

 The molecule is synthesised and stored in the neuron

 The molecule is present in the presynaptic neuron and is released into
synaptic cleft on depolarization
 When administered exogeneously as a drug,it should mimic the effects
of the endogenios neurotransmitter.
 A mechanism in the neuron or synaptic cleft acts to remove or
deactivate the neurotransmitter

SYNTHESIS AND RELEASE OF NEUROTRANSMITTERS

The neurohormones are synthesised in the neurones and their terminals from
essential aminoacids.the neuronal cells have the necessary enzymes to convert
the aminoacid to neurotransmitters by a no.of steps.the arrival of an action

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potential at the nerve terminal triggers the opening of Calcium channel
whichlead to neurotransmitter release.

The neurotransmitters are released from the axon into the synapse which is
the space between neurons.from here the neurotransmitters are received by the
dendrite or specific receptors on the surface of post synaptic cell.this process
of neurotransmission enables communication between brain cells.

The neurotransmitter molecules fit precisely into specific receptor cells

embedded in the membranes of axons and dendrites.these receptor cells either
open or close the ion channels into the cell,allowing the interchange of Na,
K,Ca.this lead to a change in the electrical charge of the cell or depolarization.
Depolarization triggers various electrical and chemical processes in the cell
caused by variety of chemicals called second messengers. They regulate the
function of ion channels,production of neurotransmitters and their release into
the synapse;thus continuing the process of neurotransmission.

The neurotransmitters are carried back from the synapse into the axon by
the process of reuptake,where they are stored or metabolized by enzymes.

Excitatory and inhibitory neurotransmitters

Based on their function neurotransmitters can be excitatory or

inhibitory.nerve cells stimulated by excitatory neurotransmitters will be
‘turned on’or stimulated to start some action.

Those nerve cells stimulated by inhibitory neurotransmitters will be ‘turned

off’causing slowing or stopping of actions.

excitator inhibitory
y
Glutamate GABA
Aspartate Glycine Adrenaline and nor adrenaline have both
Histamine Dopamine
excitatory and inhibitory functions.
ACh serotonin
ROLE OF NEUROTRANSMITTERS
IN MENTAL ILLNESS

Behaviour is the manifestation of the combined actions of potentials

emerging from masses of neurons in response to a

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 personsthought.manybehaviors and neurological symptoms are a
manifestation of disruption to the transmission of the processes.

Medications that are used to treat psychiatric disorders operate in and

around synaptic cleft and have action at the neurotransmitter level.the
discovery of new drugs has been concerned mainly with the study of
neurotransmitter that make up the chemical messenger system of the brain.

Once the neurotransmitter transfer a stimulus to the adjacent neuron,the

chemical messenger is removed from the synaptic area by any one of the
naturally occurring processes

1. The neuro transmitter leaves the area through natural diffusion of a

substance from an area of high concentration to low concentration.
2. The neurotransmitter can be broken down by enzymatic degradation
3. They can undergo reuptake and be transported back to storage in the
presynaptic neuron.

Many medications used to treat psychiatric disorders involve these 3

mechanisms.foreg.SSRIs work byinfluencing the reuptake
mechanisms,whereas monoamine oxidase inhibitors affect the degree of
enzyme degradation that occurs in the synaptic cleft.

CLASSIFICATION OF NEUROTRANSMITTERS

NN
NEUROTRANSMITTERS

AMINO ACID
BIOGENIC (GABA,GLUTAMATE,GLYCINE)
AMINES )EE

ACh monoamines histamines

m
DOPA

Indolamineseg.s catecholamines epinephrine

erotonin

norepinephrine

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I.BIOGENIC AMINES

ACETYLCHOLINE

Ach was the first neurotransmitter to be discovered. It plays a significant

role in the synaptic transmission in the central and peripheral nervous
system.

Synthesis of Ach

Ach is synthsised from acetyl Co A and choline by an enzyme known as

choline acetyltranseferase (Ch AT).ChAT is located almost exclusively in
the cytoplasm of cholinergic fibres.the acetyl Co A is derived from pyruvate
generated by glucose metabolism in the mitochondria.

Choline is derived from dietary sources and from phosphatidylcholine.it can

be supplied by Ach hydrolysis.

Ach is stored in vescicular form at the nerve terminals of cholinergic fibres.

In response to an action potential it is released by exocytosis into the
synaptic cleft ,from where it diffuses into the post synaptic site for
interaction with appropriate receptors which results in specific effects
according to the receptor type.

Receptors

The Ach receptors consist of two major groups

1. Muscarinic
2. Nicotinic

Nicotinic receptors are the first neurotransmitter receptors to be

isolated.these are classified into 2 subclasses-neuronal type and muscle
type.

Nicotinic receptors are present in the hippocampus ,cerebralcortex,thalamus

and hypothalamus superior colliculus as well as in some cholinergic nuclei
of the forebrain and brainstem.

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Muscarinic receptors :based on their pharmacological properties the
muscarinic receptors are divided into M1 and M2

The Ach binding site of the muscarinic receptor consists of a pocket

shaped indentation which is formed by the transmembrane domains.

The binding of Ach to muscarinic receptors activates different signal

transduction pathways depending on the type of muscarinic receptors.

The muscarinic receptors are expressed in the cortex,thehippocampus,the

nucleus accumbens,the striatum and amygdala.

Importance of Ach

In the CNS Ach is involved in the control of certain motor activities and in
processes coupled to learning and memory.it is the main neurotransmitter
responsible for intellectual functioning.it also play an important role in
sleep wakefulness cycle.it transfer impulses that convey calculations,
problem analysis, recognition ,learning and recall.

Several toxins can impair the functioning of Ach system.these toxins canbe
used for pharmacological purposes because of their agonistic or antagonistic
properties.

Eg-nicotine is an agonist as it activates nicotinic receptors

-atropin and scopolamine (alkaloid from the plant AtropaBelladona)

block the muscarinic receptors and are antagonists

The peripheral distribution of Ach receptors cause parasympathetic effects

like decrease in heart rate ,smooth muscle contraction and blood vessel
dilatation.

Role of Ach in psychopathology

A dysfunction of the cholinergic system occurs in some

degenerative diseases of the brain like Alzhimer’sdisease.the neurotoxic
effect of neurofibrillary tangles and beta amyloid plaques are hallmarks of
Alzhimers disease.cholinergic stimulation has role in counteracting beta
amyloid toxicity.ACh levels have been found low in clients with Alzhimers
disease and other forms of dementia.Deficiency also causes lack of

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inhibition,poor recent memory ,parkinsonism,manic behaviour and speech
blockage.

Excess amounts can cause self consciousness, overinhibition, anxiety,

psychophysiologic complaints and depression.

According to an article byNieoullon A1. cholinesterase inhibitors can

improve the cognitive capacities or attentional processes in patients and
their capability to be autonomous in daily life activities. Differences
reported between the three different major cholinesterase inhibitors could be
due to different pharmacokinetic and pharmacodynamic properties,
especially with regard to the duration and reversibility of
acetylcholinesterase inhibition. It is generally accepted that therapeutic
effects are related to cholinergic stimulation in the brain structures involved
in the regulation of cognitive and behavioral processes, with special
reference to alpha7 nicotinic receptor subtype, which are concentrated in the
cerebral cortex and hippocampal formation. Because of the involvement of
such nicotinic receptor subtype in presynaptic activation of numerous
neurotransmitters synaptic functions, general stimulation of brain structures
contributes to behavioral improvement. Data from experimental literature
also showed that acetylcholinesterase inhibitors may have neuroprotective
effects and could thus act as disease modifiers in patients, slowing the
progression of behavioral deterioration since acetylcholinesterases
themselves could contribute to the degenerative process.

RELEVANCE IN THE TREATMENT OF MENTAL ILLNESS

The most common use of anticholinergic drugs in psychiatry is in the

treatment of motor abnormalities caused by the use of antipsychotics (eg-
haloperidol).the blockade of muscarinic receptor is a common
pharmacodynamics effect of many psychotropic drugs.blockade of those
receptors cause side effects like blurred vision,dry mouth ,constipation and
difficulty in initiating urination. Excessive blockade of CNS cholinergic
receptors causes confusion and delirium.

Preclinical studies have suggested antidepressant-like effects of drugs

targeting nicotinic Ach receptors( nAChRs), with the most consistent results
observed with nAChR modulators such as varenicline and nonspecific
antagonists such as mecamylamine. These agents appear to offer the most
potential antidepressant-like efficacy when used in conjunction with other
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established antidepressant treatments. nAChR modulators also influence
neural processes that appear to mediate the behavioral effects of
antidepressants, such as hippocampal cell proliferation. (Philip NS,
Carpenter LL, Tyrka AR, Price LH.)2

HISTAMINE

Histamine was first known to be a substance released by mast cells in

response to allergen stimulation.but later identified as a physiological
mediator within different tissues including CNS.It is unable to cross blood
brain barrier.Histamine has many features in common with monoamines
like catecholamines or Indolamines like Sertonin with respect to
release,metabolic pathway and mode of action at cellular level.

Histaminergic neurons are predominantly located in the tuberal area

,posterial hypothalamus, Thalamus and forebrain.

Synthesis

The enzyme L-histidine decarboxylase (HDC) is responsible for the

synthesis of Histamine.it is formed by a single decarboxylation of L
histidine under the control of L-histidine under the control of L-histidine
decarboxylase.

Receptors

The 3 classes of Histaminergic receptors are H1 ,H2, H3.

H1 receptors

Antagonist of H1 receptors are called antihistamines which are capable of

crossing BBB. H1 receptors are mainly found in cerebral areas.

H2 receptors

In contrast to H1 antagonists, H2 antagonist are unable to cross the BBB.

(exception –Zolantidine).H2 receptors are located post synaptically and
found in areas containing large no.ofhistaminergic terminals like
hippocampus and cerebral cortex.

H3 receptors

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 They function as inhibitory, presynaptic autoreceptors which regulate the
synthesis and release of histamine. Based on the inhibitory function of
autoreceptors,H3 antagonist elicit an increase of histamine at the
extracellular site. Thus H3antagonist reveal a kind of inverse agonistic
effect.

H3 also function as heteroreceptors,inhibiting the release of

neurotransmitters like ACh, DOPA,NE and serotonin.

Importance of Histamine

It regulate cerebral circulation and permeability of cerebral vessels. Lesion

of posterior hypothalamus at site of tuberomamillarynucleas(TM) produce a
comatose like continuous sleep.

The Histaminergic innervation of the limbic system suggest that

histamine is influential on different behavioural and cognitive functions and
in the generation and maintainanceof emotional states. A competitive
antagonist of H2 receptors is the drug LSD. Some changes in the behaviour
induced by LSD might be coupled to the inactivation of H2 receptors.

Relevance in psychopathology&treatment

Selective H3 receptor antagonist have been developed-thioperamide.An

increase in Histamine is found to be effective in patients with alzhimers
diease. Cataplexy & ADHD are effective with H 3 receptor antagonist
treatment.

Study conducted by Esbenshade TA, Browman KE, Bitner RS, Strakhova

M, Cowart MD, Brioni JD.3 on H3 receptor localization , function as a
modulator of neurotransmitter release and its effects on cognitive processes
showed the following result: Blockade of centrally localized H3 receptors
by selective H3 receptor antagonists has been shown to enhance the release
of neurotransmitters such as histamine, ACh, dopamine and norepinephrine,
among others, which play important roles in cognitive processes. The
cognitive-enhancing effects of H3 antagonists across multiple cognitive
domains promotes the therapeutic approach for the treatment of attention
deficit hyperactivity disorder, Alzheimer's disease and schizophrenia.
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MONOAMINES

SEROTONIN

Serotonin, also k known as 5-hydroxy tryptamine(5HT) is synthesised

from the aminoacid L tryptophan which is a dietary amino acid located only
in the brain. tryptophan can cross the Blood Brain Barrier.

L tryptophan+O2 tryptophan hydroxylase L-5hydroxy tryptophan(5HTP)

pyridoxal PO Aromatic L aminoacid

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decarboxylase (AADC)

L-5 hydroxy tryptamine (serotonin)

Receptors

7 subtypes of serotonin receptors have been distinguished,(5HT1 -5HT2)

5HT1 receptors display high affinity to serotonin. These are mainly

expressed in the soma and dendrites of serotonergic neurons.5HT1 and 5HT2
are located on glia and muscle cells.5HT 3 receptors have low affinity to
their ligands. They are located exclusively on neurons.5HT5 receptors are
located in the cortex,olfactory bulb, hippocampus and cerebellum.5HT6 in
cortex hippocampus ,striatum, amygdala and nucleus accumbens.5HT 7 in
cortex, hippocampus,thalamus, hypothalamus, and neurons of superior
colliculus.

Importance of serotonin

Serotonin receptors in the brain can activate the hypothalamic

Pitiuitary adrenocortical axis (HPA). Direct acting serotonin agonist

,serotonin uptake inhibitors,serotonin releasers ,all increase the release of
ACTH and corticosterone.

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 Serotonin plays an important role in emotions, cognition, sensory
perception and essential biologic functions like sleep and apetite . it also
plays key role in the functions related to circadian rhythm.

Role in psychopathology

Serotonin plays important role in states of consciousness ,mood,

anxiety ,delusions and withdrawal of schizophrenia. An excess effect of
serotonin can cause hallucinations. A decreased amount of serotonin release
can cause depression,dullness and low energy. Functional deficiencies in
serotonin and nor epinephrine have been implicated in the pathophysiology
of depressive syndrome.alterations in serotonin functions have been linked
to eating and sleep disorders.

Lisergic acid diethylamide (LSD) and 3,4-

methylenedioxymethamphetamine(MDMA) or ‘ecstacy’.MDMA block the
uptake of serotonin and induce massive release of serotonin.

Relevance in the treatment of mental illness

The mechanism of action of antidepressants is related to their ability to

inhibit the reuptake of neurotransmitters like serotonin and nor
epinephrine.SSRIs and SNRIs are used for the treatment of depression.

Another serotonergic drug used for the treatment is L tryptophan,ingestion

of which can increase the concentration of serotonin.it was withdrawn from
market in1990 in USA by food an drug administration(FDA) because a
contaminant from the production process at one particular manufacturing
site caused an eosnophilia myalgia syndrome in some patients.

The potency of some new medications for migraine headache is related to

their ability to block serotonin transmission.descending serotonergic
pathways are important in central pain control.

5HT1 agonist, Buspirone is used for the treatment of anxiety.

CATECHOLAMINES

DOPAMINE

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 Dopamine is the most important neurotransmitter because it effects a
large no.of neurological functions including cognition, motor and
neuroendocrine functions.

The precursors of dopamine are Phenylalanine and Tyrosine .they are able
to cross BBB,whereas Dopamine do not. Tyrosine can be synthesised from
Phenylalanine by the activity of Phenylalanine hydroxylase.

Synthesis

The biosynthesis of dopamine takes place within the nerve terminals ,in the
cytosol from which the neurotransmitter is transported to presynaptic
vescicles. Dopamine is synthesised from tyrosine in a 2 step process.

Phenylalanine phenylalanine hydroxylase tyrosine tyrosine hydroxylase DOPA

Dopamine

decarboxylase

DOPAMINE

Since dopamine is synthesised and stored in the presynaptic

vescicles,cellbodies of dopaminergic neurons contains relatively low
amounts of dopamine.

Release of dopamine

Dopamine is released by the action potential through a calcium dependent

mechanism into the synaptic cleft.the Ca influx through voltage dependent
Ca channel triggers the fusion of the vescicles with the presynaptic
membrane.a pore is formed from which dopamine is released into the
synaptic cleft. It then diffuses across the synaptic cleft and binds to post
synaptic receptors.the outcome is an activation or inhibition of the post
synaptic neuron. The dopaminergic signal is finally terminated by removal
of dopamine

from intersynaptic cleft. This removal involves specific re uptake

mechanism into the pre synaptic terminal where it can be stored and reused.

receptors

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 Most dopamnergic neurons are located post synaptically,but some pre
synaptically. These pesynaptic receptors are called autoreceptors. They
monitor the extra cellular dopamine concentration and modulate the impulse
dependent release and synthesis of dopamine.a blockade of these receptors
facilitate the synthesis and presynaptic release of dopamine,while their
stimulation has the opposite effect. The autoreceptors are found at the nerve
terminals,as well as on the soma and dendrites of most dopaminergic
neurons. Stimulation of autoreceptors located at the nerve terminals result in
inhibition of DA release wheras stimulation of somatodendritic autoreceptor
decreases the firing rate of dopaminergic neurons.

The D1 group consists of D1 and D5 receptors.D2 consists of D2,D3 andD4

receptors;and the autoreceptors.

D1 receptors appear to be most abundant in brain,expressed in the striatum ,

amygdala, thalamus ,mesencephalon, hypothalamus and hindbrain. The
absence of D1 receptor in adults is an indication that this receptor type lacks
a role as an autoreceptor.

D2 receptors are expressed in the striatum, mesencephalon ,spinalcord,

hypothalamus and hippocampus. The 2 isoforms of D2 receptors are
‘long’(D2L) and ‘short’(D2S); or D2A and D2B.

D2S are abundant in posterior cerebral cortex, amygdala,hypothalamus and

the brain stem. D2L receptors are located in the extrapyramidal basal
ganglia.

D3 receptors have structural and pharmacological similarities with D2

receptors. They are widely distributed in the basal forebrain,the olfactory
tubercle,nucleas accumbens,striatum but infrequent in limbic and
extrapyramidal regions where D2 receptors are found in high densities.

D4 receptors are expressed in the frontal cerebral cortex, hippocampus,

thalamus,striatum, basal ganglia and cerebellum. In contrast to D1,D2, D3
receptors which have little affinity to Clozapine (dopamine receptor
antagonist), D4 receptors display moderate affinity to this substance.

D5 RECEPTORS have very restricted distribution in the brain.they are

expressed exclusively in the hippocampus and thalamus.

IMPORTANCE OF DOPAMINE

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 Dopamine is involved in the initiation and execution of movement and
regulation of emotional responses , thinking and decision making.it also
modulates the arterial blood flow, higher mental functions like cognition
and learning and in anxiety related behavior. Therefore dopaminergic
system serve as a target for antipsychotic drugs,especially in schizophrenia
treatment. Over activity of Dopamine is hypothesised in many symptoms of
schizophrenia.

The classic domain for dopamine substitution is Parkinsonism, where the

degeneration of substantia nigra is the cause of the disease. The tubero
infundibular system cause release of prolactin. An increase in dopamine
activity results in an inhibition of prolactin release. Thus dopamine
constitutes prolactin inhibiting factor.

Excess amount of dopamine is found to cause disorganised thinking,loose

association, stereotype behaviour etc.. It is also significant in mood
disorders .DA activity is low in depression and high in mania. Low level of
DA is observed to Parkinsons disease, movement disorders, poor impulse
control problems with abstract thinking etc.

Role in psychopathology

Dysfunction of dopaminergic transmission influences a veriety of

neurological and psychiatric disorders. Any hyperactivity of dopaminergic
system leads to an accumulation of the neurotransmitter in the synaptic
cleft. Dopamine hyperactivity have been found to be linked to some
psychotic disorders,including hallucination and manic state.

It is also considered to be involved in a no. of fear related disorders like

phobia ,panic attacks post traumatic stress disorders,OCD,and generalized
anxiety disorders.

Dopamine is also significant in mood disorders. Dopamine activity is low in

depression and high in mania.low levels of dopamine is observed in
parkinsons disease, movement disorders,poor impulse control problems with
abstract thinking etc.

Relevance in treatment of mental illness

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In the past the potency of antipsychotic components has been correlated
with their affinity to D2 receptors. Blockade of D2 receptors is associated
with increased efficacy of antipsychotics. A new class of highly effective
antipsychotics called serotonin- dopamine antagonist block predominantly
5HT2 and D2 receptors. They can treat both positive and negative
symptoms of schizophrenia.

Nicotine stimulates the release of Dopamine and Glutamate.

Epidemiological studies found that smokers have a reduced risk of
developing Parkinsons disease,Alzhimers disease and ulcerative colitis.
Many drugs of abuse like Cocaine and Amphetamines also cause
dopamine release.

The D2 receptors are involved in the causation of schizophrenia and

parkinsons disease.there is direct correlation between the dose and affinity
of neuroleptics for D2 receptors and inhibition of their responses by D2
antagonists. Antipsychotics block DA in the post synaptic cell.

EPINEPHRINE AND NOR-EPINEPHRINE

The Nor epinephrine and Epinephrine system are referred to as nor

adrenergic and adrenergic systems respectively.although these two are
discussed together Nor epinephrine is more important and abundant

Synthesis

Nor epinephrine is derived from Tyrosin,a dietary aminoacid.

tyrosinetyrosine hydroxylase DOPADOPA carboxylase Dopamine

Dopamine

beta hydroxylase

Norepinephrine

Excess of catecholamines inhibit the activity of Tyrosine hydroxylase in a

negative feedback loop.

Receptors

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 NE is released from nerve varicosities.the receptor are collectively called
adrenoceptors,and occur in the plasma membrane of the neurons from the
central and peripheral nervous system. The 3 receptor types are alpha1,
alpha2 &beta.

Importance of norepinephrine

NE levels fluctuate with sleep and wakefulness. It plays a role in changes in

levels of attention and vigilance,and in regulation of mood. It has role also
in anxiety and affective disorders.

Role in psychopathology

NE receptor activation can be either excitatory or inhibitory.NEergic system

seems to be directly involved in depression, mood stabilization, drive and
motivation. Antidepressive agents prolong the half life of catecholamines
either by inhibition of their reuptake or by decreasing the metabolic rate.
(eg.by inhibiting MAO). Post synaptic α2 receptor downregulation seems to
be prevalent in depression. Decreased NErgic receptor sensitivity and
increased turnover has been noted in patients with anxiety disorder and post
traumatic stress disorder.NE has been suggested to be involved in anti
seizure effects.NE play an important role in learning and memory. It is
depleted in clients with Alzhimers disease and Korsakoffs syndrome,
contributing to symptoms of long term and short term memory loss and
limited learning ability.

Excess of NE can cause anxiety hyperalertness, paranoia, loss of apetite.

Deficit amounts show dullness low energy and depression.

Relevance in the treatment of mental illness

The Psychiatric drugs that are associated with NE are :

 Classic antidepressants
 Tricyclic drugs
 MAOI

Some drugs like Cocaine and tricyclic drugs block the reuptake of NE into
the presynaptic neuron and thus leads to an increased concentration of
extracellular NE. The consequence is a prolongation of the post synaptic action

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of NE on its receptors. This mechanism is thought to be responsible for
psychostimulating and euphorizing effects of antidepressants and Cocaine.

NE is metabolized by intra mitochondrial MAO. It is involved in the

degradation of NE. thus MAOI elevate the neuronal level of NE.

II. AMINOACID ACID NEUROTRANSMITTERS

GABA

GABAergic cells are located in the striatum, substantia nigra and cerebellum. It
does not cross the BBB.

Synthesis

GABA is synthesised from Glutamate. It plays an important role in

neuromuscular coordination, deficiencies can cause clumsiness and lack of co-
ordination.

Importance of GABA

Drugs that increase the GABA function,such as benzodiazepines,are used to

treat anxiety and to induce sleep.

Receptors

GABA is released from the terminals of specific inhibitory neurons. The 3 types
of receptors are GABAA, GABAB, GABAC .

GABAA receptors have 3 binding sites. First site binds with GABA. 2 nd is a
specific site for binding BZD and the third binding site is specific for
Barbiturates.

Role in psychopathology

It has an important role in causing anxiety disorders. The choreatic movements

that characterises Huntingtons disease is associated with loss of GABA activity.
Decreased GABA activity is involved in the development of seizure and
sensorimotor function.

Relevance in the treatment of mental illness

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Benzodiazepines ,barbiturates, and other anticonvulsants act primarly through
GABAergic mechanisms. A drug,Progabide is a GABA receptor agonist with
good brain penetration and has anticonvulsant activity.BZD show
anticonvulsive ,anxiolytic, sedative and muscle relaxant properties. They are
also used for the treatment of anxiety and sleep disorders. Some BZD act as
agonist, some as antagonist.

GABA binds to GABAA receptors in the basolateral amygdala and inhibits

anxiety responses. Anxiolytic compounds like diazepam show agonistic effects
on GABA. Flumazenil mediates antagonist like effects by blocking the effects
of agonists.

GLYCINE

It is a major inhibitory neurotransmitter in the spinalcord and brainstem.the

main function is epileptogenesis.

Hyperekplexia (startle disease)is a rare neurological disorder characterised by

an exaggerated response to external stimuli. This response is typically
accompanied by complete muscular rigidity. susceptibility to disease is
increased by emotional tension ,nervousness ,fatigue and expectation of being
frightened. Symptoms of this disease are present from birth, the reason why it
is called ‘stiff baby syndrome’ with infants displaying severe muscular rigidity.
It may be misdiagnosed as epilepsy.treatment is by the administration of BZD
with clonazepam.

GLUTAMATE AND ASPARTATE

Brain Glutamate and Aspartate are derived solely by local synthesis. Glutamate
is formed by Kreb’s cycle. It is synthesised in nerve terminals and accumulate
in synaptic vescicles.

receptors

NMDA, AMPA, Kainate receptors. A receptor common to both Glutamate

and Aspartate, NMDA records new experiences for learning and future use as
memory. These are the first receptors to be destroyed in chronic alcoholism
.NMDA receptors have been implicated in the pathophysiology of
schizophrenia.Glutamate neurotransmitter receptor system is poorly reacting to

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psychotherapeutic agents. Too much NMDA receptor activity kills neurons and
too little activity induce psychosis. Phencyclidine (PCP) is an important
substance of abuse acting at glutamate receptors.

PEPTIDE NEUROTRANSMITTERS

Eg: endogeneous opioids

Corticotropin releasing factor (CRF)

A peptide is a short protien consisting of about 100 amino acids. As many

as 300 peptides neurotransmitters may be identified in human brain. Though
they appear in very low concentrations in the CNS,they are very potent. They
play a second “messenger”role in neurotransmission,they modulate the message
of the nonpeptide neurotransmitters. They are involved in the activation and
regulation of responses to stress and injury such as pain, perception and reflex
reaction.

Role in psychopathology

‘Substance P’ found in afferent sensory motor neurons hypothesised to

contribute to symptoms of Alzhimers and mood disorders.Endorphins and
enkephalins are widely distributed in the CNS. Excess of Endorphin cause
insensitivity to pain ,catatonia like disorder, auditory hallucinations, and
impaired memory. Hypersensitivity to pain and stress,inability to experience
pleasure are found in deficiency. CRF has role in modulating the response to
internal and external stress.

RELEVANCE IN TREATMENT OF MENTAL ILLNESS

Endogenous opioids have remarkable analgesic and psychologic effects. The

discovery of alkaloid morphine in 1806 led to the development of extensive
pharmacological assays for opiate agents. Morphin and heroin bind to
endorphin and enkephalin receptors on presynaptic neurons, blocking the
release of neurotransmitter and reducing pain. Substance P is found in the pain
transmission pathway. Blocking its release by morphine reduce pain.CRF
antagonist is thought to be useful in treating depression.
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Conclusion

Knowledge of neurotransmitters is essential because even a single dose of adrug

affecting this system may cause relief of symptoms or have side effects.
Psychiatric mental health nurses have a significant role in assessing symptoms
and administering medications. Many nursing interventions designed to effect
changes in functions like sleep, diet ,exercise , stress management affect these
neurotransmitters directly or indirectly.

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