Summary NSG 552 Psychopharmacology Exam 1 Study Guide LATEST 2024.
DOPAMINE
• Dopamine belongs to the family of catecholamines. It is a neurotransmitte... [Show More] r.
• Hormones, Epinephrine and Norepinephrine (other catecholamines) are derived from Dopamine
• Dopamine plays a significant role in learning, goal-directed behavior, regulation of hormones, motor
control.
DOPAMINE SYNTHESIS
Phenylalanine (amino acid from diet) -> phenyalanine hydroxylase -> Tyrosine -> Tyrosine hydroxylase ->
DOPA -> Dopa decarboxylase -> Dopamine
KEY POINT: Dopamine is synthesized directly from tyrosine or indirectly from phenylalanine
• Dopamine is packed and stored into synaptic vesicles via the vesicular monoamine transporter (VMAT2)
and stored until its release into the synapse.
• When dopamine is released during neurotransmission, it acts on 5 types of postsynaptic receptors (D1-D5).
• A negative feedback mechanism exists through the presynaptic D2 receptor which regulates the release of
dopamine from the presynaptic neuron.
• Any excess dopamine is cleared out
o Presynaptically by Dopamine transporter (DAT)
o VMAT2 will take excess DA and store it in the synaptic vesicles for future neurotransmission
• Excess dopamine is broken down within the presynaptic neuron by monoamine oxidase A (MAO-A), MAOB and extracellularly (outside the neuron) by catechol-o methyltransferase (COMT).
• All antipsychotic drugs can reduce dopaminergic neurotransmission.
DOPAMINE RECEPTORS
• Dopamine neurotransmission is perpetuated via G protein-coupled receptors categorized into two broader
subtypes
• D1 – like family:
o Includes subtypes D 1 and D5
o Activation is coupled to Gs ; activates adenylyl cylcase which leads to increase in concentration of
cAMP
• D2 – like family:
o Includes D2, D3 and D4
o Activation is coupled to Gi ; inhibits adenylyl cyclase leading to decrease in concentration of cAMP
o Also open K channels & closes Ca influx
• DAT (dopamine transporter) and VMAT2 are DA receptors that also regulate DA neurotransmission
• Presynaptic D2 autoreceptors are “gatekeepers” and provide negative feedback input. When D2 receptors are
NOT bound to DA DA release. When D2 receptors bind to DA inhibit DA release
o Location: Striatum, substantia nigra, pituitary
o Located presynaptic and postsynaptic
FGAs and Neurotransmitters
• Mesolimbic pathway: involved in pleasure and reward. Blocking D2 in this pathway by FGA’s not only
treats positive symptoms, but it blocks the reward mechanism and can cause apathy, lack of motivation, lack
of interest and the ability to feel joyful
• Negative symptoms of psychosis are due to low dopamine in the mesocortical pathway. When FGA’s block
D2 receptors here, negative symptoms such as blunted affect, lack of pleasure, reduced social interaction
can worse
• Dopamine inhibits prolactin release in the tuberoinfundibular pathway. When FGA’s bind to D2 in this
pathway, there is an increase in serum prolactin levels leading to galactorrhea, infertility or low sex drive.
NSG 552 Psychopharmacology Exam 1 Study Guide
LATEST 2024.
NSG 552 Psychopharm exam 1 study guide.
• The degree of D2 receptor binding in the mesolimbic pathway needed for antipsychotic effects is close to
80% , while D2 receptor occupancy greater than 80% in the dorsal striatum is associated with EPS and in
the pituitary is associated with hyperprolactinemia. This creates a very narrow therapeutic window Between
the threshold for antipsychotic efficacy and that for side effects in terms of a D2 binding.
• If D2 receptors in the nigrostriatal DA pathway are blocked chronically, it can cause TD. D2 receptors are
hypothesized to become super sensitive or to upregulate (i.e.increase in number) perhaps in an attempt to
overcome drug induced blockade of D2 receptors in the striatum. After long term treatment the D2 receptors
apparently cannot or do not reset back to normal even when conventional antipsychotics are discontinued.
This leads to tardive dyskinesia that is irreversible, continuing whether conventional antipsychotic drugs are
administered or not
• In addition to binding to D2 in all pathways, FGA’s also block muscarinic M1 cholinergic receptors, leading
to blurry vision, dry mouth, constipation and cognitive blunting (Stahl, p.138). FGAs that caused more EPS
are the agents that have weak anti cholinergic properties, whereas those FGAs that cause fewer EPS are the
agents that have stronger anti cholinergic properties. Dopamine normally inhibits acetylcholine. If dopamine
can no longer suppress acetylcholine release then acetylcholine becomes overly active. Therefore, EPS is a
result of dopamine deficiency and excess acetylcholine. Drugs with anticholinergic actions will diminish the
excess acetylcholine activity caused by removal of dopamine inhibition when dopamine receptors are
blocked by FGAs. Thus, EPS is reduced. This occurs in the nigrostriatal dopamine pathway.
• The use of anticholinergic drugs with an FGA does not lessen the ability of the FGA to cause tardive
dyskinesia.
• Other properties of FGA’s is the blockade of histamine receptors which leads to weight gain and drowsiness
(Stahl, 2013). Blockade of alpha1 receptors can have cardiovascular effects, such as hypotension and
drowsiness.
• An old-fashioned way to sub classify FGAs is low potency versus high potency. Low potency agents tend to
have more of the additional properties such as blockade of muscarinic M1-cholinergic receptor, blockade of
histamine and alpha1-adrenergic receptors. [Show Less]
