32: Drug Action on Dopamine Receptors Flashcards
Explain the mechanism of dopamine after signaling in/across the synaptic cleft.
- A part of dopamine crosses the synaptic cleft and binds to dopamine receptors in the postsynaptic membrane.
- After activation of the receptors, the dopamine receptors drive a series of downstream signaling for physiological functions.
What are the two types of dopamine receptors?
D1-like receptors (D1, D5)
D2-like receptors (D2, D3, D4)
Explain the result of dopamine receptor activation on adenylyl cyclase.
D1-like receptors - when dopamine binds –> AC is activated (more cAMP)
D2-like receptors - when dopamine binds –> AC is inhibited (less cAMP)
Explain the results of dopamine activation of D1-D1, D2-D2, and D1-D2 receptors.
In the brain, what are the pathways that dopamine contributes to?
mesocortical
mesolimbic
nigrostriatal
tuberoinfundibular
Name which human diseases are associated with decreased dopamine receptors.
- parkinson’s disease
- hyperprolactinemia
- restless leg syndrome
Name the two types of dopamine receptor agonists.
Ergoline type
Non-ergoline type
Describe the role of dopamine in parkinson’s disease development.
Dopamine neurons in the brain slowly break down and can eventually die.
* With decreasing levels of dopamine, the brain can’t function properly –> abnormal brain activity –> parkinson’s symptoms
Describe the two fundamental ways to treat parkinson’s disease.
- replace dopamine
- mimick dopamine’s effect (using dopamine agonists)
Describe characteristics of patients with parkinson’s disease.
- depressive symptoms/disorders are common
- **increased anxiety **–> accentuate symptoms of the disease
- treatment of non-ergoline agonists have been suggested - D2-like agonists.
- not ergoline agonists –> bc of risk of cartilage formation in heart valves.
Describe the association between dopamine and hyperprolactinemia.
Hyperprolactinemia is the presence of abnormally high levels of prolactin in blood.
* dopamine is a prolactin-inhibiting factor –> lowers prolactin-releasing factors synthesis and secretion through D2-like receptors.
* Treatment: ergoline-derived agents
Describe the association between dopamine and restless leg syndrome.
RLS is a long-term disorder that causes strong urge to move one’s leg with unpleasant feeling.
* dopamine-dependent disorder
* stimulation of dopamine receptors –> increase dopamine levels –> decrease RLS symptoms
* treatment: non-ergoline agonists
Describe the human diseases that are associated with increased dopamine functions.
- schizophrenia
- bipolar disorder
- huntington’s disease
Name the two types of dopamine receptor antagonists.
- first generation antipsychotics (more adverse reactions, cheaper)
- second generation antipsychotics (less adverse reactions, more expensive)
Describe the association between dopamine and schizophrenia.
Alterations of dopamine receptors and abnormalities in glutamatergic signaling are involved in the genesis of psychotic and cognitive symptoms.
* treatment: second generation antipsychotics
Describe the association between dopamine and bipolar disorder.
AKA manic depression - extreme mood swings that include extreme highs and lows.
* treatment: mood stabilizers, antipsychotics, antidepressants, antipsychotics-antidepressants, antianxiety medications
Describe the association between dopamine and huntington’s disease.
Huntington’s disease is a rare, inherited disease that causes the progressive breakdown (degeneration) of nerve cells in the brain.
* unusually high levels of dopamine –> cause chorea (involuntary jerking or writhing movements)
* treatment: drugs to control movement and antipsychotics
Cabergoline
Drug action:
Target protein:
Therapeutic indication:
Drug action: dopamine receptor agonist - ergoline type
Target protein: D2-like receptors
Therapeutic indication: hyperprolactinemia
Bromocriptine
Drug action:
Target protein:
Therapeutic indication:
Drug action: dopamine receptor agonist - ergoline type
Target protein: D2-like receptors
Therapeutic indication: hyperprolactinemia
Pramipexole
Drug action:
Target protein:
Therapeutic indication:
Drug action: dopamine receptor agonist - non-ergoline type
Target protein: D2-like receptors
Therapeutic indication: Parkinson’s disease & restless leg syndrome
Rotigotine
Drug action:
Target protein:
Therapeutic indication:
Drug action: dopamine receptor agonist - non-ergoline type
Target protein: D2-like receptors
Therapeutic indication: parkinson’s disease & restless leg syndrome
Fluphenazine
Drug action:
Target protein:
Therapeutic indication:
Drug action: dopamine receptor antagonist - first gen
Target protein: D2-like receptors
Therapeutic indication: Huntington’s disease
Risperidone
Drug action:
Target protein:
Therapeutic indication:
Drug action: dopamine-receptor antagonist - second gen
Target protein: D2-like receptors
Therapeutic indication: Schizophrenia & bipolar disorder
Olanzapine
Drug action:
Target protein:
Therapeutic indication:
Drug action: dopamine receptor antagonist - second gen
Target protein: D2-like receptors
Therapeutic indication: schizophrenia & bipolar disorder
