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Goal of Presentation:
The goal of this presentation is to provides an introduction to
the functional organization of the CNS and its synaptic
transmitters as a basis for understanding the actions of the
neurologic and psychiatric drugs described in subsequent
lectures.
Marc Imhotep Cray, M.D. Modified from Brody’s Human Pharmacology, 2010 4
CNS Pharmacology
Lecture 1
SMOOTH MUSCLE,
EFFECTOR SKELETAL
CARDIAC MUSCLES
ORGANS MUSCLES
AND GLANDS
VOLUNTARY
INVOLUNTARY
Monosynaptic
Marc Imhotep Cray, M.D. Pre & Post Ganglionic Fiber
CNS Pharmacology
Lecture 1
Overview
The properties of the CNS, like the properties of peripheral organs
(ANS), are mediated by neurochemical transmitters acting at
receptor sites
Overview (2)
As in the ANS, the CNS consists of opposing neurotransmitter
systems
Overview (3)
The etiology of CNS functional disorders is often difficult to
determine
For example:
It is now recognized that clinical depression and clinical anxiety
are biochemically distinct from normally experienced feelings of
sadness or apprehension (respectively)
Schizophrenia is now known to consist of what are known as
positive and negative symptoms
Pain is now known to be multifaceted
Neuronal atrophy is implicated in conditions in which it was not
previously suspected
Marc Imhotep Cray, M.D. 10
CNS Pharmacology
Lecture 1
Overview (4)
Drugs targeted to CNS disorders, like drugs used for
conditions affecting the PNS but to a much larger extent,
are subject to abuse--sometimes by patients but more
often by non-patients
Such abuse can adversely affect the availability of
these drugs (such as opioids for relief of severe
pain) to patients in need
Neurotransmitters
in the CNS
Marc Imhotep Cray, M.D. Wecker L, et al. Brody’s human pharmacology : molecular to clinical 5th ed. 24
CNS Pharmacology
Lecture 1
Most Well Studied Neurotransmitters
of the Brain
1) Norepinephrine
2) Dopamine
3) 5-Hydroxytryptamine (5-HT, Serotonin)
4) Acetylcholine
5) Gamma-amino butyric acid (GABA)
6) Excitatory Amino Acids (EAA), Glutamate
7) The Endogenous Opioids
8) Other Neuropeptides
2) Dopamine
Dopamine is synthesized from Dopa, the
hydroxylated congener of the amino acid
tyrosine
Dopamine (2)
Dopamine (DA) receptors are classified as D1 & D2
Both subtypes reside in numerous regions of the brain
No specific D1 agonists have been identified
Activation of either subtype inhibits the rate of neuronal
firing
Dopamine (3)
In the CNS, dopamine serves as a neuromodulator
Two groupings can be distinguished:
the family of D1-like receptors (comprising subtypes D1 and D5) and
the family of D2-like receptors (comprising subtypes D2, D3, and D4)
Dopamine (4)
Particularly important dopaminergic pathways include:
1) the nigrostriatal pathway (from substantia nigra to
striatum)
2) neurons of the chemoreceptor trigger zone (CTZ) of the
medulla, which controls vomiting, and
E.g., Apomorphine is a D2 agonist=emesis-inducing
3) projections from the hypothalamus to the intermediate
lobe of the anterior pituitary, which regulate prolactin
release
In other words PIF is mediated via DAergic neurons
Dopamine (5)
Antipsychotic drugs inhibit dopamine-stimulated adenylate cyclase
(usually associated with D1 receptor activation) and block D2
dopamine receptors
suggest psychoses may result from overstimulation of dopamine
receptors
Parkinson's Disease, is caused by too little dopaminergic input from
the substantia nigra into the striatum
Loss of the nigrostriatal dopamine neurons results in a relative
decrease in dopamine input (inhibitory) compared to
acetylcholine input (excitatory)
Serotonin (3)
Depression, attention deficit disorder and headaches
have been attributed to serotonergic imbalances
Serotonin (4)
Excess 5-HT can result from accidental or intentional overdose
of drugs that directly activate serotonin receptors or, more
commonly,
drugs that indirectly enhance serotonin levels
by inhibiting presynaptic neuronal reuptake of serotonin
by inhibiting serotonin breakdown by monoamine oxidase
E.g., selective serotonin reuptake inhibitors,
nonselective serotonin reuptake inhibitors, and
MAOIs
4) Acetylcholine (Ach)
The synthesis, release and degradation of acetylcholine was learned in
PNS study
Acetylcholine binds to both muscarinic (AChm ) and nicotinic (AChn )
receptors throughout the brain
(Drugs which mimic or modify acetylcholine neurotransmission were also covered in PNS)
Glutamate (2)
Excitatory amino acids such as glutamate are thought to
be important in learning, memory and other brain
functions
N-Methyl-D-Aspartate (NMDA)
Glutamate is an excitatory neurotransmitter, and NMDA
receptors (NMDAR) are one type of glutamate receptor
THE END
Lectures/discussions to follow:
2. Sedative-Hypnotic and Anxiolytic Drugs
3. Antiepileptic Agents
4. Antidepressants
5. Drugs Affecting Bipolar Disorder
6. Antipsychotic Agents
7. Drugs Affecting Movement Disorders and Other Neurodegenerative Disorders
8. CNS Skeletal Muscle Relaxants
9. Analgesics and Anesthetics