Dopaminergic and Serotonergic (Exam 1) Flashcards
Serotonergic
Serotonin Neurotransmitter
Serotonin
Monoamine found in CNS and enterochromaffin cells
Serotonergic receptors
5HT1-5HT7
Dopaminergic
Dopamine Neurotransmitter
Dopamine
Monoamine neurotransmitter found in brain, adrenal medulla, and GI tract
Dopaminergic Receptors
D1-D5
Indolamines
Serotonin, melatonin
MAO-A
Norepinephrine and serotonin breakdown
MAO-B
Dopamine breakdown
Serotonin 5HT1 (A, B, D, E, F, P) Receptors
Gi
Serotonin 5HT2 (A, B, C) Receptors
Gq
Serotonin 5HT3 (A, B, C, D, E) Receptors
LGIC (mostly Na+)
Serotonin 5HT4 Receptors
Gs
Serotonin 5HT5 (A) Receptors
Gi
Serotonin 5HT6 Receptors
Gs
Serotonin 5HT7 Receptors
Gs
Tryptophan
Synthesizes 5HT
5-HIAA
Major metabolite of serotonin excreted in urine
SERT (Serotonin Transporter)
Reuptake into presynaptic terminal
Where are 5HT1 receptors located?
Presynaptically as autoreceptors
CNS Serotonin
Tryptophan actively transported into brain by LAT1 to synthesize serotonin
PNS Serotonin
Synthesized by enterochromaffin cells of GI tract
How is serotonin in the brain produced?
By neurons originating in raphe nuclei
Serotonin signaling in the brain is important for (5)
Mood Regulation
Eating Behaviors
Emetic Response
Cognition
Sleep-wake
Mood Regulation
Reduction in serotonergic signaling may lead to depression
Activation of 5HT2A Receptors
Causes hallucinations/delusions
Eating behaviors
Drugs that enhance serotonergic signaling may cause weight gain
5HT2 agonists can lead to weight loss
Emetic (Vomiting) response
Signaling through 5HT3 in chemoreceptor trigger zone enhances this
Serotonergic Signaling in Spinal Cord
Reduce pain perception
Enteric Nervous System (ENS)
Controls serotonergic signaling in the GI tract
5HT4 Activation
Enhanced intestinal peristalsis and faster gastric emptying
Platelet Effect
Activation of 5HT2A receptors on platelets weakly enhances platelet aggregation
Vasculature Effect
Activation of serotonergic receptors on blood vessels primarily leads to vasoconstriction
Drugs that inhibit SERT
Slightly increase bleed risk by reducing platelet serotonin storage
SSRIs
Inhibit serotonin transporter
Serotonergic syndrome (SS)
Excessive serotonergic signaling
May occur due to drug interaction
Symptoms of SS
Agitation, confusion, restlessness
Vasoconstriction, nausea, vomiting
Fever
Muscle twitching and spasms
SERT Inhibitors (SSRIs)
Enhance serotonergic signaling in brain
Used for depression
5HT3 Receptor Antagonists (Setrons)
Reduce nausea and vomiting by antagonizing receptor in GI tract and at CTZ
Treats nausea and vomiting
5HT1B/1D Receptor Agonists (Triptans)
Cause vasoconstrictions of cerebral vascular
Treats migraines
CNS Dopamine Synthesis
Tyrosine and L-DOPA must be actively transported across BBB by transporter LAT1
Dopamine cannot cross BBB
PNS Dopamine synthesis
Neuroendocrine cells found in tissues synthesize dopamine
Homovanillic Acid (HVA)
Major metabolite for dopamine
Dopamine D1, D5 Receptors
Gs
Dopamine D2, D3, D4 Receptors
Gi
DAT (Dopamine Transporter)
Responsible for uptake in storage vesicles
A = Nigrostriatal Pathway
Increased dopamine can lead to hyperkinesia
Decreased dopamine can lead to bradykinesia
B = Mesolimbic Pathway
“Reward Pathway”
Euphoria and feelings of reward
Increased dopamine leads to hallucinations
C = Mesocortical Pathway
Increased dopamine can increase cognition and emotional affect
Decreased dopamine impairs cognitive and emotional affect
D = Tuberoinfundibular Pathway
Dopamine inhibits prolactin release
Decreased dopamine leads to galactorrhea and gynecomastia
Parkinson’s Disease (PD)
Loss of dopamine-containing substantia nigra neurons
Pathophysiology of PD
Balance between dopaminergic and cholinergic signaling is disrupted
D2 Receptor Antagonists
Reduce hallucinations in mesolimbic pathway - schizophrenia
Reduce nausea/vomiting in CTZ
Increase gastric motility
Addictive Drugs
Enhance dopaminergic release in mesolimbic pathway
DAT/NET/VMAT Inhibitors (Amphetamines)
Increase release of DA and NE in brain
Treatment of ADHD
NET Inhibitors (SNRIs)
Enhance serotonergic and adrenergic signaling in CNS
Treats depression and neuropathic pain
MAO Inhibitors
Non-selective inhibitors breakdown serotonin, NE, and DA
Treats depression
D2 Receptor Antagonists
Reduces hallucinations and delusions
Treats schizophrenia
Thyrotropin-releasing hormone (TRH)
Stimulates prolactin secretions while dopamine inhibits
Dopamine receptor agonists
Activate dopaminergic receptors in nigrostriatal pathway
Treats PD and Restless Leg
Levodopa/Carbidopa
Increases dopamine in CNS
Treats PD
MAO-B inhibitors
Reduce breakdown of dopamine
Treats PD
COMT inhibitors
Reduce breakdown of dopamine
Treats PD
Cardiovascular Dopamine
Activates D1 receptors leading to vasodilation
High concentrations activate beta1 and alpha1 receptors
Kidney Dopamine
Activation leads to increased sodium and water exce4rtion
GI tract Dopamine
Activation decreases gastric motility
Dopamines affinity for dopaminergic and adrenergic receptors
Dopamine receptors»_space; beta»_space; alpha
Dopamine can act as a substrate for
NET