DOPAMINE, bromocriptine and pergolide.pptx

Dopamine

1. DOPAMINE RECEPTORS
PHARMACOLOGY 1

By:-

Manisha

M.Pharm. (Pharmacology)

Deptt. of Pharmaceutical sciences
M.D. University Rohtak, 124001

2. Contents

Dopamine

Biosynthesis of dopamine
Functions of dopamine
Dopaminergic pathways
Dopamine receptors
Dopamine agonists
Dopamine antagonists
Dopamine related diseases

3. Dopamine

* Dopamine is a monoamine neurotransmitter
that upon binding to a dopamine receptor
releases a variety of downstream signals.

4. Biosynthesis of dopamine

* Dopamine is synthesized in a restricted set of cell type
called dopaminergic neurons.

" The metabolic pathway is: -

L-Tyrosine

L-DOPA

Dopamine Receptors

Dopamine

5. Functions of dopamine

> Some of its notable functions are in:
= Movement

" Memory

" Pleasurable reward

* Behavior and cognition
Inhibition of prolactin production
" Nausea and vomiting

6. Dopaminergic pathway

* Nigrostriatal pathway- substantia nigra to the caudate
putamen (dorsal striatum) , primarily associated with motor
acivity

* Mesolimbic pathways- VTA to the limbic areas of the
brain (accumbens, ventral striatum and amygdala), associated
with cognition and behavior

* Mesocortical pathway-VTA to the cortex (medial,
prefrontal, cingulate and entorhinal cortex), associated with
reward and schizophrenia

* Tuberoinfundibular pathway- arcuate and
peer nuclei of the hypothalamus to the intermediate
obe of the pituitary and the median eminence, inhibitory
control of prolactin

7. Prefrontal
cortex

Nucleus

ne
accumbens =
Hypothalamus i

Pituitary

DD Mescconical pattrway

Mesolimbic pathway
I Nigrostriata! pathway
M Tuverointundibular pathway

Ventral
tegmental
area

Putamen

Caudate
nucieus

~ Substantia
nigra

8. Dopamine receptor

" Dopamine receptors are a class of G protein-
coupled receptors

Sorarcha ride EXTRACELLULAR

palmicoyl
group
y SA

mernbrane-spannäng
a tels

INTRACELLULAR

9. Dopamine Receptor Subtypes

+ Da- like family:

* Includes subtypes D1 and Ds

* Activation is coupled to G ; activates adenylyl cyclase
which leads to increase in concentration of cAMP

* These receptor genes do not contain introns in their
coding genes

> D2- like family :

* Includes D2, D3 and D4

» Activation is coupled to G; inhibits adenylyl cyclase
leading in decreased concentration of cAMP

* Genes that encodes these receptors contain introns

10. Locations and MOA of dopamine
receptors

Receptors

Locations

Response

D, Like

D

1

caudate/
putamen,
nucleus
accumbens,
olfactory
tubercle,
hypothalamus,
thalamus,
frontal cortex
adenylyl
cyclase
activated

hippocampus,
thalamus,
lateral
mamillary
nucleus,
striatum,
cerebral
cortex (all
low)
adenylyl
cyclase
activated

D, like

D

caudate/
putamen,
nucleus
accumbens,
olfactory
tubercle,
cerebral
cortex (low)

adenylyl
cyclase
inhibited

nucleus
accumbens
, olfactory
tubercle,
islands of
Calleja,
cerebral
cortex
(low)
adenylyl
cyclase
inhibited

frontal cortex,
midbrain,
amygdala,
hippocampus,
hypothalamu
s, medulla (all
low), retina

adenylyl
cyclase
inhibited

11. Dopamine agonists

= Act directly on dopamine receptors and
mimic the endogenous neurotransmitter.
Bromocriptine
Pergolide
Lisuride
Cabergoline
Ropinirole
Pramipexole

12. Dopamine antagonists

Prochlorperazine
Perphenazine
Trimethobenzamide
Metoclopramide
Droperidol

13. Dopamine related diseases

+ Parkinson’s disease

Caused by the loss of dopaminargic neurons in the
substantia nigra.

* Signs and symptoms-
Rigidity, tremors, bradykinesia

> Schizophrenia
Hyperactive dopaminergic signal transduction
* Signs and symptoms-
Hallucinations, delusions, disorganized thinking and
speech

14. Drug addiction

"= Dopamine is the primary neurotransmitter involved in the
reward pathway in the brain.

Recreational drugs (cocaine and substituted amphetamines)

Y

inhibit the dopamine transporter (DAT), the protein responsible for
removing dopamine som the neural synapse.

v
synapse floods with dopamine

Y

increases dopaminergic signaling (particularly in nucleus accumbens)

y

mediates the "rewarding" stimulus of drug intake.

15. Attention-deficit hyperactivity
disorder

Due to decreased level of dopamine
* Signs and symptoms

Impaired cognitive control, attentional control, inhibitory
control, forgetting things or missing details

16. References

" Marsden A. Charles, “Dopamine: the rewarding years”,
British Journal Pharmacology, published online 2008 Jan
9, doi- 10.1038/sj.bjp.0706473

" Missale Cristina, Nash S. Russel, * Dopamine
Receptor:From structure to function“, Physiological
Reviews, Published 1 Jan 1998, vol. 78, no. 1, 189-225

" Brisch Ralf, Saniotis Arthur,“The Role of Dopamine in
Schizophrenia fron a Neurobiological and Evolutionary
Perspective: old fashioned but still in vogye”, Published
online 2014 May 19, doi. 10.3389/fpsyt 2014.00047