Pharma Mind Flashcards
Presynaptic: Drugs acting on the:
• Synthesis(#2),
storage-(#3),
metabolism(#4) and
release of neurotransmitters(#5).
At synaptic cleft:
• uptake/reuptake to pre-synaptic neuron or glial cell(#6)
• Degradation (#7)
Postsynaptic: Drugs act either:
• As neurotransmitter agonist or blockers on post-synaptic
receptors (#8)
• Act on the post-synaptic ion-channels/receptors …leading to ionic
conduction(#9)..example GABA-receptors.
• Act on the post-synaptic G-protein coupled metabotropic
receptors..…leading to intra-cellular changes(#9)..example
DOPAMINERGIC-receptors
Definition: Glutamate
acts on postsynaptic glutamate receptors, which can be either:
Excitatory neurotransmitter .
It is released from pre-synaptic vesicles into the synaptic cleft by Ca 2+-
dependent exocytosis
acts on postsynaptic glutamate receptors, which can be either ionotropic
(iGluR like NMDA,AMPA or kainate) or metabotropic (mGluR)
GABA and Glycine
Both are inhibitory
neuro-transmitters,
– typically released from
local interneurons.
– Glycine from spinal
cord and brain stem.
– Interneurons for GABA
from CNS, including the
spinal cord.
– Some in the spinal cord
release both GABA and
glycine.
– Both lead to influx of Cl
ions…. CNS inhibition
Norepinephrine
– Most noradrenergic neurons are
located in reticular formation.
– Most regions of the CNS receive
diffuse noradrenergic input. All
noradrenergic receptor subtypes are
metabotropic.
MOA:
– Norepinephrine can increases SNS
(sympathomimetic activity). – It is a MONOAMINE…so will help in
treatment of depression and
ADHD**.
Serotonin/ 5-Hydroxytryptamine
– Most 5-hydroxytryptamine (5-
HT, serotonin) pathways
originate from neurons in the
pons and upper brainstem.
– 5-HT has been implicated in the
regulation of virtually all brain
functions, including
– perception, mood, anxiety, OCD
pain, sleep, appetite,
– temperature, neuroendocrine
control, and aggression.
– If decreased 5-HT,disturbance
in above functions
(e.g.DEPRESSION,OCD), we can
use various group of
drugs(SSRIs) to increase action
of 5-HT to normal levels and
thus treat the disease.
Histamine
• In the CNS, histamine is exclusively made by neurons in the tuberomammillary
nucleus (TMN) in the posterior hypothalamus.
• These neurons project widely, where they modulate arousal, attention, feeding behavior, and memory
• histamine receptors (H1 to H4), all of which are metabotropic.
Centrally acting ANTIHISTAMINES are generally used for:
their sedative
properties and antagonism of H1 receptors is a common side effect of many drugs including some tricyclic antidepressants and antipsychotics.
Peripherally acting, ANTIHISTAMINES
are generally used for treating allergic
reactions.
Dopamine
• D1 – D5 ; all of them are metabotropic. • Dopamine exerts a slow inhibitory action on CNS neurons.
• In the substantia nigra, activation of D2 receptors opens K+ channels via
the Gi coupling protein.
• NORMAL DOPAMINE in body:
• Abnormal/INCREASED DOPAMINE:
• DECREASED DOPAMINE:
• Reward, Pleasure, motivation and
attention.
• Schizophrenia.(…so
we can use dopamine-antagonist drugs to treat it).
• Parkinson’s syndrome and
depression etc. (…so we can use dopamine-agonist drugs to treat these
conditions)
Acetylcholine
• Eight major CNS nuclei of acetylcholine
neurons – These include neurons in the
neostriatum, the medial septal
nucleus, and the reticular
formation that appear to play an
important role in cognitive
functions, especially memory.
– Presenile dementia of the
Alzheimer type is reportedly
associated with a profound loss of
cholinergic neurons.
Neurotransmitter sites of actions of various DRUGS used in psychiatric disorders
- Antidepressants. MAO-Is
TCAs SSRIs - Anxiolytics - Anti-psychotics
Glutamate Hypothesis
– There is evidence that Acute-Stress increases release of glutamate and
patients get depressed during stress
– so by reducing glutamatergic transmission we can treat “stress-induced
depression”
A. The Dopamine Hypothesis for Schizophrenia:
excessive dopaminergic activity plays a role in the disorder. Drugs that increase dopaminergic activity.. DOPAMINE AGONISTS, either increase schizophrenia or produce psychosis. For example:
*Levodopa (release dopamine),
**Bromocriptine (direct dopamine receptor agonist)].
Most ANTI-PSYCHOTIC DRUGS are dopamine-antagonists which strongly block postsynaptic D2.
B. The Glutamate Hypothesis of Schizophrenia:
Decreased amount of Glutamate in the body leads to more chances of schizophrenia. Antagonists of NMDA receptor(drugs decreasing glutamate action) such as **phencyclidine (PCP) **and ketamine (non-competitive) produce much more “schizophrenia-like” symptoms than do dopamine agonists.
C. The Serotonin Hypothesis of Schizophrenia:
– - SEROTONIN AGONISTS are Hallucinogens; such as LSD (D-lysergic
acid diethylamide) and mescaline that act by stimulating 5-HT2A- receptor means increased levels of serotonin leads to s/s of schizophrenia.
– - NEW ATYPICAL ANTIPSYCHOTIC AGENTS leads to blockade of 5-
HT2A-receptor(inverse-agonist of 5-HT2A) .it is a key factor in the mechanism of action of main class of atypical anti-psychotic drugs; clozapine is the prototype.
