PHAR 300 Lecture Notes - Lecture 1: Beta Blocker, Histamine Receptor, Insomnia
7 Jun 2018
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Department
Course
Professor
PHAR300
Benzodiazepines
-drugs to treat mental disease / disorder
-still a lot of unknown, but we have pretty effective drugs
-psychopharmacology : drugs that treat neurological disorders
-in the past, mental disorders used to be attributed to demons…
-most serious psychiatric disorder is schizophrenia : the individual is out of touch with reality for
a certain part of time (different degrees)
-prevalence : ~1%
-familial distribution : genetic component, for identical twins, the risk of developing
schizophrenia is 48% => there is more than only a genetic component, and we unfortunately
don’t understand everything
-we know some areas (prefrontal cortex), the time of development (~early adulthood)
-neuroscience is very important in examining what goes
wrong
Pharmacologist’s view of the brain
-how cells communicate with each other, how do 2 neurons
talk to each other ?
-many steps along the way -> something can go wrong at any
point in this pathway and drugs can be active at any point as
well to try to counteract the abnormality in the mental
disorder
Developing antipsychotic drugs
-drugs for schizophrenia were a true revolution (analogy to
contraceptives)
-we can see that with the beginning of widespread use of
psychopharmaceuticals, the number of patients confined to
hospitals drastically decreased from 1950s to 2000s =>
tremendous benefit of these drugs
-drugs discovered in treating schizophrenia act on
dopamenergic pathways in the brain
-dopamine is the major transmitter in the pathway
controlling motor function
-mesocortical pathway is mainly involved in
schizophrenia
-schizophrenia : elevated dopamine in these regions ->
specific receptors : D2 for dopamine
-amine is released in the synapse
-dopamine can be taken back up by transporters
and can be stored in vesicles
-dopamenergic receptors are G-protein coupled
receptors which can stimulate or inhibit in this
case cAMP and lead to signal transduction and
gene expression
-D2 receptor is inhibitory -> drugs that work for
schizophrenia act on D2 receptors
1
-D2 receptors are found post-synaptically on the dopaminergic synapse, as well as pre-
synaptically on other types of pathways => drugs possibly also act on these pathways
(more than one mechanism) in addition to the direct effect on dopaminergic pathway
-chlorpromazine : first effective neuroleptic drug
-member of the Phenothiazines that block dopamine D2 receptor
-also acts in other locations : inhibits many receptors and pumps (alpha1 adrenergic
receptors, norepinerphine reuptake…) => side effects
-new antipsychotic agents were developed to be more selective, and act specifically on the
D2 receptor (such as Trifluoperazine)
-amphetamine and cocaine enhance release / block the reuptake of dopamine and foster
symptoms of schizophrenia
-effectiveness of antipsychotic drugs correlates to block D2 receptors (amount we need to use to
have antipsychotic activity) => D2 receptor is involved in schizophrenia
Depression
-varies in intensity
-noradrenaline and seretonin release are boosted by antidepressant drugs
-mechanisms of action of antidepressant drugs
-increase the amount of transmitter in the synapse => increase the transmission through the
aminergic pathway
-3 categories
-Monoamine Oxidase Inhibitors (MAOIs) : decrease the metabolism of the amines
(noradrenaline, serotonin…) -> increase the level of the transmitters to act on the
post-synaptic receptors (either more stored in the vesicles or more in the synapse)
-Tricyclic Antidepressants (TCAs) : interfere with the reuptake of the amines in the
pre-synaptic terminal -> more amines in the synapse [5 HT -> for serotonin and
noradrenaline]
-many side effects : they block various receptors in addition to having an effect on
the reuptake pumps (they block adrenergic receptors -> vascular side effects : the
2
Document Summary
Drugs to treat mental disease / disorder. Still a lot of unknown, but we have pretty effective drugs. Psychopharmacology : drugs that treat neurological disorders. In the past, mental disorders used to be attributed to demons . Most serious psychiatric disorder is schizophrenia : the individual is out of touch with reality for a certain part of time (different degrees) Familial distribution : genetic component, for identical twins, the risk of developing schizophrenia is 48% => there is more than only a genetic component, and we unfortunately don"t understand everything. We know some areas (prefrontal cortex), the time of development (~early adulthood) Neuroscience is very important in examining what goes wrong. Many steps along the way -> something can go wrong at any point in this pathway and drugs can be active at any point as well to try to counteract the abnormality in the mental disorder. Drugs for schizophrenia were a true revolution (analogy to contraceptives)
