Neurohumoral transmission in CNS- The term neurohumoral transmission designates the transfer of a nerve impulse from a presynaptic to a postsynaptic neuron by means of a humoral agent e.g. a biogenic amine, an amino acid or a peptide.

1. Neurohumoral
Transmission In Central
Nervous System
BY- SANCHIT DHANKHAR
M.PHARMACY

2. Overview:-
 Neurohumoral Transmission
 Steps Involved in Neurohumoral Transmission
 Introduction.
 GABA
 Glycine.
 Glutamate.
 Serotonin.
 Dopamine.
 Histamine.

3. Neurohumoral Transmission
 Neurohumoral transmission refers
to the transmission of nerve impulse
through synapse & Neuroeffector
junction by the release of humoral
(chemical) substance e.g. a
biogenic amine, an amino acid or a
peptide.
 Information is communicated from
Nerve to Nerve, from Nerve to
Effector Organ, by the process
called Neurohumoral Transmission

4. Steps Involved in Neurohumoral Transmission
 Impulse Conduction.
 Neurotransmitter Release.
 Neurotransmitter Action on Post junction Membrane.
 Post junction Activity.
 Termination of Neurotransmitter Action.

5. Impulse Conduction
 Refers to Passage of an Impulse along nerve fibre.
 After receiving an information from a Peripheral Organ through Sensory
Nerve.
 CNS sends message or Impulse through efferent autonomic nerve.
 Impulse Conduct by generating Action Potential.
 Action Potential is self propagating & is conducted along Axonal Fibre.
Note: Resting Potential is - 70mv ( negative Inside Neuron)
Depolarization – Influx of Na+ Repolarization – Efflux of K+
Repolarization is Shorter than Depolarization.

6. Neurotransmitter Release
 Depolarisation leads to stimulation and
opening of voltage sensitive Ca+
Channel.
 Ca+ helps in fusion between Axoplasmic
Membrane and Synaptic Vesicle (Store
house of Neurotransmitter)
 Neurons release by Exocytosis.

7. Neurotransmitter Action on Post -
Junctional Membrane
 The Released Transmitter combines with
specific receptors on the post junctional
membrane
 Depending on its Nature induces an :-
1. Excitatory Post Synaptic Potential.
2. Inhibitory Post Synaptic Potential.

8. Post Junctional Activity
 Excitatory Post synaptic Potential generates a propagated post
Junctional Action Potential, which results :-
1. Nerve impulse in Neurons
2. Contraction in Muscles
3. Secretions in Glands
 An Inhibitory Post Synaptic Potential Stabilize Post junctional
membranes and Resist Depolarization stimuli.

9. Termination of Transmitted Action
 It is either Locally Degraded or Partly taken back into Pre
junctional Neuron by active Reuptake.
It Can also be explained easily by the following Diagram :-

11. CNS- Central Nervous System
 It consist of Brain and Spinal Cord

15. Gamma Aminobutyric Acid (GABA)
 Gaba is the main inhibitory Neurotransmitter in CNS, Synthesized in Brain.
 It acts by binding to specific receptor on both Pre and Post synaptic
Membrane.
 Synapses using GABA are referred to as GABAergic synapses.

20. Glycine
 Simplest Amino acid, semi essential Amino acid.
 Major Inhibitory neurotransmitter in CNS also known as Inhibitory chloride
Channel Protein.
 They are Present in abundance in Spinal cord.
 Glycine receptor is a member of Nicotinic receptor superfamily.
 To prevent Tissue Injury.
 To enhance anti – oxidant Capacity.
 To promote protein synthesis and wound healing.
 Used in Spasticity
 For biosynthesis of Heme, Creatinine & Glutathione.
Function

21. Synthesis
 serine + tetrahydrofolate → glycine +
N5,N10-Methylene tetrahydrofolate + H2O

22. Receptor
 The Glycine receptor responsible for inhibition is a Cl- Channel.
 It is Ionotropic in Nature & is Pentamer made up of two subunits.
a) The ligand- Binding Alpha Subunit.
b) The Structural Beta Subunit.

23. Glutamate
 They are Excitatory Amino Acid.
 Principal excitatory neurotransmitter in CNS, stored in Neuronal cell
membrane.
 Glutamate comes into the CNS mainly by glial cells and by Kreb’s Cycle.
 Responsible for neural communication, memory formation, learning and
regulation.
 Glutamate Comes from glial cells in the neuron.
 In the neurons the glutamine is converted into glutamate with the help of
glutaminase enzyme
 Glutamate is stored in the synaptic vesicles.
 From synaptic vesicles glutamate release by the process of exocytosis
which is Ca+ dependent.
Synthesis

26. Receptors
 Glutamate receptors are synaptic receptors located primarily on the
membranes of Neuronal cells.
 Glutamate (glutamic acid ) is abundant in the human body, but particularly
in the nervous system and especially prominent in the human brain where
it is the body’s most prominent neurotransmitter, the brain’s main inhibitory
neurotransmitter.
 Glutamate receptors are responsible for the glutamate – mediated
postsynaptic excitation of neural cells, and are important for neural
communication, memory formation, learning, and regulation.

29. SEROTONIN
 The scientific name for serotonin is 5-hydroxytryptamine, or 5-HT
 It is a monoamine neurotransmitter.
 About 90% of is found/localized in the intestines: the rest in brain and
platelets.
 The level of 5-HT in whole blood is in the range of 65–250 mg/ml
 It is popularly thought to be a contributor to feelings of well-being and
happiness it is a key mediator in the physiology of mood, vascular function
and gastrointestinal motility.
 This explains the number of therapeutic agents that act targeting the
serotonergic system such as: 5-HT3 antagonists, SSRIs and triptans

30. Disturbance in the Serotonin levels may cause :-

33. ACTION AND FUNCTIONS OF
SEROTONIN

34. PERIPHERAL MEDIATED
PHYSIOLOGICAL FUNCTIONS OF 5-
HT RECEPTORS In periphery
 Peristalsis
 Vomiting
 Platelet aggregation and haemostasis
 Inflammatory mediator
 Sensitization of nociceptors (Pain receptors)
 Microvascular control

35. Central effects of serotonin receptor
 Neuronal inhibitions through decrease of cAMP
 Behavioral effects
 sleep mood
 feeding thermoregulatory
 anxiety
 Cerebral vasoconstrictions

36. Serotonin pathways in the Brain
 Serotonin pathways that are located in the brainstem area “the Raphe
nuclei” these neurons control muscle activity, 5-HT receptors trigger
vomiting.
 The serotonin neurons in frontal cortex, regulate cognition and memory.
 The serotonin neurons in the hippocampus regulate memory.
 The serotonin neurons in the other limbic areas regulate mood. ( basal
ganglia and cerebral cortex). SSRI’s work in this pathway.

39. Drugs acting on 5-HT receptors

40. Drugs acting on serotonergic
neurotransmission

41.  MAO inhibitors ;-
Monoamine oxidase is a key enzyme for serotonin, dopamine and
norepinephrine inactivation. MAO inhibitors prevent inactivation of
monoamines within a neuron, causing excess neurotransmitter to diffuse
into the synaptic space. This class of agents is used in the treatment of
depression (phenelzine, tranylcypromine, selegiline) and Parkinson’s
disease (selegiline).
Dietary restrictions (because of tyramine toxicity) limit their widespread
use.
 Inhibitors of serotonin storage ;-
They interfere with the ability of synaptic vesicles to store monoamines;
displace serotonin, dopamine and norepinephrine from their storage in
presynaptic nerve terminals.
Agents that share this mechanism of action include amphetamine,
methylphenidate and modafinil

43. The Side Effects of Selective
Serotonin Reuptake Inhibitor’s
 Dry mouth
 Sweating
 Headaches
 Sedation
 Dizziness
 Nausea
 Somnolence (Sleepeness)
 Insomnia
 Diarrhea

44. Serotonin agonist

45.  Serotonin receptors agonists have wide clinical applications, from
treatment of depression to abortive medications for migraine headache.
According to the receptor they activate, they can be divided into:
 5-HT1A agonists ;-
Buspirone is a partial 5-HT1A agonist used clinically for the treatment of
anxiety and depression.
 5-HT1B and 5-HT1D agonists ;-
The “triptans” are a drug class useful as abortive medication for the
treatment of acute migraine headaches. They are very effective in causing
cranial vasoconstriction and decreased release of neuropeptides involved
in “sterile inflammation”.

46.  5-HT2C agonist ;-
Trazodone was previously believed to be a 5-HT2C receptor antagonist.
However, recent publications report that trazodone would behave as a 5-HT2C
agonist. This drug is used generally as somnorific.
 5-HT4 agonists ;-
Cisapride is a serotonin and cholinergic agonist used as a prokinetic drug, it
was withdrawn from the U.S. market because of cardiovascular toxicity.
 Non-selective agonists ;-
Ergotamine activates a more than one subtype of 5-HT receptor, it binds to 5-
HT1A, 5-HT1D, 5-HT1B, D2 and norepinephrine receptors. Its vasoconstrictor
effect makes it a suitable treatment for migraine attacks.
LSD is a 5-HT1A, 5-HT2A, 5-HT2C, 5-HT5A, 5-HT5, 5-HT6 agonist that has
psychedelic properties.

47. 5-HT2 Antagonist
Ketanserin is a 5-HT2A/2C antagonist used for the treatment of hypertension. In addition to its serotonin
antagonism, it has affinity for alpha-1 receptors, which may contribute to its antihypertensive effect.

48.  Clozapine is an atypical antipsychotic drug that acts as 5-HT2A/2C
receptor antagonist with high affinity for dopamine receptors, the
involvement of 5-HT has possibly increased the chances of greater
efficacy and reduction in negative symptoms of schizophrenia.
 Agomelatine is a new antidepressant with agonist action at the melatonin
receptor and antagonism at the 5-HT2C receptor.
 5-HT3 antagonists --
This class includes drugs such as ondansetron, palonosetron and others.
These agents are particularly useful in the treatment of chemotherapy
induced nausea and vomiting .

49. Serotonin Syndrome – What Happens When Your
Serotonin Levels Are Too High?

50. Tips for naturally boosting serotonin
 1. Get morning sunlight, its more intense and this can boost your body’s
production melatonin.
 2. Get plenty of exercise, researchers have found that exercise boost
serotonin
 3. Reduce your stress (both physical and emotional), prolonged stress
produce adrenaline and cortisol which interfere with serotonin
 4. Eating foods that are high in protein because of high percentage of
tryptophan
 5. Also food containing carbohydrates as they produce insulin which helps
tryptophan go into the brain

51. Dopamine
 Dopamine belongs to the family of catecholamines
 Hormones Epinephrine and Norepinephrine (other catecholamines) are
derived from Dopamine.
 Significant role in learning, goal-directed behavior, regulation of hormones,
motor control

53. Storage and Release

54. Metabolism

55. Receptors
 Metabotropic G-protein coupled receptors
 D1 – like family:
 Includes subtypes D1 and D5
 Activation is coupled to Gαs ; activates adenylyl cylcase which leads to
increase in concentration of cAMP
 D2 – like family:
 Includes D2, D3 and D4
 Activation is coupled to Gαi ; inhibits adenylyl cyclase leading to decrease
in concentration of cAMP

57. Physiological roles

58. Major Dopamine pathways

59. Control of movement
 The largest Dopamine tract in the brain
which contains about 80% of brain’s
dopamine in the nigrostriatal system.
 Assisted in learning coordinated
movements.

61. Parkinson’s Disease
 Substantial loss of Dopamine in the striatum (70 – 80%)
 Loss of dopamine neurons in other systems also (Mesolimbic,
Mesocortical and Hypothalamic systems)
 Treatment strategy includes increasing dopamine levels by administering ;-
 Dopamine precursor : Levodopa (l-dopa)
 (b) Peripheral decarboxylase inhibitors : Carbidopa,.
 (c) Dopaminergic agonists: Bromocriptine, Ropinirole, Pramipexole
 (d) MAO-B inhibitor: Selegiline
 (e) COMT inhibitors: Entacapone, Tolcapone
 (f) Dopamine facilitator: Amantadine

63. Schizophrenia
 Defective dopamine neurotransmission – relative excess of central
dopaminergic activity
 An increase in DA function in the mesolimbic system and a decreased
function in the mesocortical DA systems
 Behavior similar to the behavioral effects of psychostimulants
 Antipsychotics such as chlorpromazine, bind to D 2 dopamine receptors
and reduced positive psychotic symptoms

66. Parmacological effects

67. Histamine
Introduction
 Histamine is a biogenic amine found in many tissues, including mast cells,
basophils, lymphocytes, neurons, and gastric enterochromaffin-like cells.
 It is an autacoid—that is, a molecule secreted locally to increase or decrease the
activity of nearby cells.
 Histamine is a major mediator of allergic and inflammatory processes.
 It also has significant roles in the regulation of gastric acid secretion,
neurotransmission, and immune modulation.

69. Storage and Release
 Histamine synthesis and storage can be divided into two “pools”:
 a slowly turning over pool
 a rapidly turning over pool
 The slowly turning over pool is located in mast cells and basophils.
 Histamine is stored in large granules in these inflammatory cells, and the
release of histamine involves complete degranulation of the cells.
 The rapidly turning over pool is located in gastric ECL cells and in
histaminergic CNS neurons.
 These cells synthesize and release histamine as required for gastric acid
secretion and neurotransmission, respectively.

75. Thank You