1.
Neurohumoral
Transmission in CNS
K Ravi kumar
M.Pharm 1st semester Reg no: 170604017
Department of pharmacology
Manipal university

2.
CONTENTS
• Introduction
• Neurohumoral transmission
• Neurotransmitters
• Neurodegenerative diseases
• Conclusion
• References

3.
NEUROHUMORAL
TRANSMISSION IN
CNS

4.
Anatomic organisation of the cns

5.
Chemical mediators in the CNS
• Small molecules
• Biogenic amines
• Serotonin
• Dopamine
• Histamine
• Epinephrine
• Norepinephrine
• Amino acids
• Glutamate
• Aspartate
• GABA
• Glycine
• Others
• Acetylcholine
• Nitric oxide
• Neuromodulators
• Neuropeptide-y
• Substance-p
• Lipid mediators
• prostaglandins
• Growth factors
• Nerve growth factor
• Brain derived growth factor

6.
Chemical mediators in the CNS
Mediator type Examples Targets Mainfuntional role
Small molecule
mediators
Glutamate ,GABA,
Acetylcholine,
Dopamine ,5HT
Ligangated
ion channels
G-PCR
Fast & slow synaptic
neurotransmission
Neuromodulation
Neuropeptides Substance P,
Neuropeptide Y
Endorphins
G-PCR Neuromodulation
Lipid mediators Prostaglandins
Endocannabinoids
G-PCR Neuromodulation
Neutrophins
Cytokines
Nerve growth
factor
Kinase-linked
receptors
Neuronal growth ,
survival & functional
plasticity

7.
Amino acid neurotransmitters

8.
Metabolism and release of aminoacids

9.
Glutamate Synthesis

10.
Glutamate pathway
MEMANTINE
REMACIDINE
PIRACETAM

11.
NMDA receptor

12.
Ionotropic glutamate receptors
NMDA AMPA Kainate
Agonists Glutamate
Aspartate
Glycine
D-serin
Glutamate
AMPA
Quisqualate
Glutamate
Antagonists Ap-5,CPP NBQX NBQX
ACET
Modulators Polyamines Cyclothiazide
Piracetam
Channel blockers Phencyclidine
Ketamine
Remacidine
Location Postsynaptic
Glial cells
Post synaptic
Glial cells
Pre & post synaptic
Function Synaptic plasticity
Excitotoxicity
Fast epsp Fast epsp
Presynaptic inhibition

13.
Metabotropic glutamate receptors
Group 1 Group 1 Group 1
mGlu1 , mGlu5 mGlu2 , mGlu3 mGlu4 , mGlu6 ,
mGlu7 mGlu8
G-PCR Gq Gi/Go Gi/Go
Agonist DHPG
CHPG
LY354740 L-AP4
Antagonist LY367385a
S-4-CPG
LY341495 CPPG
Location somatodendritic Somatodendritic
& Nerveterminal
Nerveterminals

14.
γ-AMINOBUTYRIC ACID

15.
GABAergic pathway
PICROTOXIN
VIGABATRIN
TIGABINE

16.
GABA Receptors

17.
Glycine
• Glycine particularly present in high concentrations in
the grey matter of spinal cord

18.
Properties of Inhibitory amino acid receptors
GABAA GABAB Glycine
Agonist Muscimol
Gaboxadol
Baclofen Glycine
Taurine
Antagonist Bicuculline
Gabazine
2-hydroxy-
saclofen
Channel
blocker
Picrotoxin Strychnine
Effector
mechanism
Ligandgated chloride
channel
GPCR Ligandgated chloride
channel
Location GABAergic neurons Pre & post
synaptic
Postsynaptic
mainly in brain stem
&spinal cord

19.
BIOGENIC AMINES

20.
Dopamine pathway

21.
Dopamine pathway in Brain

22.
DOPAMINE Receptors
D1 D5 D2 D3 D4
D1 D2
Corpus striatum
Hippocampus
hypothalamus
Substantia nigra
Limbic system
Midbrain
Medulla oblongata
Excitatory Inhibitory

23.
5HT PATHWAY

24.
28978077
Metoclopramide
Ergotamine
Methysergide
Granisatron Ergotamine

25.
Serotonin pathway in the brain

26.
5HT receptors
5HT1 5HT2 5HT3 5HT4
GPCR GPCR GPCRIONOTROPIC
Inhibitory Excitatory Ligandgated Excitatory
cAMP IP3 & DAG NA+, K+ cAMP

27.
Receptors Location Agonists Antagonists
5HT1A
5HT1B
5HT1D
5HT1F
CNS
Vascular smooth
muscles
Blood vessels
Uterus, heart, GIT
Buspirone
Ergotamine
5-CT
Trip tans
Trip tans
Ergotamine
Methiothepin
Ergotamine
5HT2A
5HT2B
CNS,PNS
Smooth muscles
Gastric fundus
LSD
Methysergide
Cyproheptadiene
5HT3 PNS,CNS Chloromethyl
biguanide
Granisetron
Ondansetron
5HT4 GIT Metoclopramide

28.
 Neurodegenerative diseases
• Parkinsonism
• It is defined as a neurodegenerative disorder of
extrapyramidal Nigrostriatal pathway
• Therapy : MAO & COMT inhibitors
• Alzhiemers
• loss of cholinergic neurons results in shrinkage of the brain
and other pathological conditions
• Therapy : Nootropic agents
• Antiamyloid antibodies
• NMDA receptor blocker

29.
 Huntington
 Depletion of GABA neurons
 Therapy : GABA-B Agonist
 Ischaemic Brain Damage
 Decrease blood supply results in hypoxia
 Therapy : NMDA receptor blocker

30.
CONCLUSION
• The optimistic view is that a better understanding of
the particular functions of the many molecular subtypes
of these targets, and the design of more subtype-
specific ligands, will lead to future breakthroughs.

31.
References
1. Bleakman, D., Lodge, D., 1998. Neuropharmacology
of AMPA and kainate receptors. Neuropharmacology
37, 187–204. (Review giving molecular and functional
information on these receptors),
2. Barnard, E.A., 2000. The molecular architecture of
GABAA receptors. In: Möhler, H. (Ed.), Pharmacology of
GABA and glycine neurotransmission. Handbook of
experimental pharmacology 150. Springer-Verlag, Berlin,
pp. 79–100. (Authoritative review on the molecular subtypes of
GABAA receptors

32.
3. Bylund, D.B., 2007. Receptors for norepinephrine and
signal transduction pathways. In: Ordway, G.A., Schwartz,
M.A., Frazer, A. (Eds.), Brain norepinephrine. Cambridge
University Press, London.
Head, G.A., Mayorov, D.N., 2006. Imidazoline receptors,
novel agents and therapeutic potential. Cardiovasc.
Hematol. Agents Med. Chem. 4, 17–32. (Provides an update
on the elusive imidazoline receptors