DOPAMINE

  • INTRODUCTION:
  • Dopamine belongs to the family of catecholamines
  • Hormones, Epinephrine and Norepinephrine (other catecholamines) are derived from Dopamine & all acts through Seven pass receptor
  • Significant role in learning, goal-directed behavior, regulation of hormones, motor control
  • Dopamine is the major neurotransmitter in substantia nigra
  • Slow IPSP in autonomic is generated by Dopamine
DOPAMINE RECEPTORS:
  • Metabotropic G-protein coupled receptors
  1. D1 – like family:
  2. Includes subtypes D1 and D5
  • Activation is coupled to Gs ; activates adenylyl cylcase which leads to increase in concentration of cAMP
  1. D2 – like family:
  2. Includes D2, D3 and D4
  • Activation is coupled to Gi ; inhibits adenylyl cyclase leading to decrease in concentration of Camp
  1. Also open K channels & closes Ca influx
  2. Dopamine receptor with inhibitory action is D2
DOPAMINERGIC PATHWAYS:
  • Mesolimbic Pathway
  • Mesocortical Pathway
  • Nigrostriatal Pathway:The efferent fiber bundle of the substantia nigra transmits dopamine to Corpus striatum
  • Tuberoinfundibular Pathway
  • Incertohypothalamic Pathway
  • Medullary Periventricular
  • Retinal
DRUGS MODIFYING DOPAMINERGIC TRANSMISSION:

Mechanism Drug Effect Use
Synthesis L-DOPA ↑ Synth Parkinsons disease
2 methyl-p- tyrosine Inhibits tyrosine hydroxylase expts
Carbidopa , Benserazide Inhibit dopa decarboxylase Parkinsonism
Storage Reserpine, Tetrabenzine Disrupt storage Tranquilizer
MAO inhibitors Enhance storage
Release Amphetamine, Tyramine, Mazindole Release dopamine on receptors Anorectic, CNS stimulant

nactivation of uptake Amphetamine, Cocaine, CNS stimulant Anorectic
BenztropineBenzhexol Parkinson's disease
Inactivation of metabolism Iproniazid, Tranylcypromine, Nonselective MAO inhibitors
Selegiline MAO inhibitors Parkinson's disease
EFFECT OF DOPAMINE:
  • Schizophrenia:
  1. Defective dopamine neurotransmission – relative excess of central dopaminergic activity
  2. An increase in DA function in the mesolimbic system and a decreased function in the mesocortical DA systems(D1 predominates)
  3. Behavior similar to the behavioral effects of psychostimulants
  • Parkinson’s Disease
  1. Parkinson’s sufferers have low levels of dopamine
  2. L-dopa raises DA activity
  3. People with Parkinson's develop schizophrenic symptoms if they take too much L-dopa
  4. Treatment strategy includes –increasing dopamine levels, nerve grafting with dopamine containing cells and deep brain stimulation
  5. Bromocriptine,Ropinerole & Pramipexole are dopaminergic agonists used for parkinsonism
  • Other motor disorders:
  1. Huntington’s disease
  2. Tourrette’s syndrome
  3. D2 Blockers –Chlorpromazine , Haloperidol
  • Attention deficit hyperactivity disorder
  1. Altered dopamine neurotransmission is implicated in attention deficit hyperactivity disorder (ADHD)
  2. Some of the most effective therapeutic agents for ADHD are psychostimulants-> methylphenidate and amphetamine: increase both dopamine and norepinephrine levels in brain. Dopamine and Addiction:
  3. Almost all dependence producing drugs mesolimbic dopaminergic projection to ventral striatum -- mechanisms for addiction
  4. Psychostimulants such as Cocaine and Amphetamine -- alter dopamine activity in brain
  5. Inhibits secretion of prolactin by acting on D2 receptors.
  6. Role of
  • Dopamine in renal system:
  1. Dopamine at 1-2 Microgram/ Kg/ min produces Renal vasodilatation
  2. Dopamine is preferred in treatment of shock because of Renal vasodilatory effect
  3. Selectively activates dopamine specific receptors in the renal and splanchnic circulation.
  4. Increase blood flow in these region.
  5. Increase GFR.
  6. Increase in urinary Na excretion
  7. Effect of dopamine on kidney is blocked by Haloperidol
  • Heart and Vasculature:
  1. Dopamine Causes Vasoconstriction
  2. At low concentrations, circulating DA primarily stimulates vascular D1 receptors, causing vasodilation and reducing cardiac afterload.
  3. DA is able to activate adrenergic receptors to further increase cardiac contractility.
  4. The net result is a decrease in blood pressure and an increase in cardiac contractility.
  5. Drug most useful in cardiogenic shock is Dopamine
  • Anti-insulin
  • Analgesic
  • Role in apoptosis
  • Memory
  • Immune

Exam Question
  • The strategy for therapy for dopamine deficiency in the substantia nigra of individuals with Parkinson’s disease is indicated by Provision of metabolites in the tyrosine pathway Neurotransmitter related to schizophrenia pathology is dopamine
  • The efferent fiber bundle of the substantia nigra transmits dopamine to Corpus striatum
  • Dopamine is the major neurotransmitter in substantia nigra
  • Slow IPSP in autonomic is generated by Dopamine
  • Adrenaline, noradrenaline and dopamine act through Seven pass receptor
  • Dopamine shows Positive ionotropic effect
  • Dopamine Improves renal perfusion
  • Dopamine Causes Vasoconstriction
  • Effect of dopamine on kidney is blocked by Haloperidol
  • Dopamine is preferred in treatment of shock because of Renal vasodilatory effect
  • Prolactin secretion will be inhibited by Dopamine
  • Bromocriptine,Ropinerole & Pramipexole are dopaminergic agonists used for parkinsonism
  • Dopamine Neurotransmitter is depleted in Parkinson's disease
  • Drug most useful in cardiogenic shock is Dopamine
  • Dopamine is preferred over dobutamne in treatment of renal shock because of Renal vasodilatory effect
  • Anti-psychotic drugs act through Dopamine D4 receptor blockade
  • Dopamine at 1-2 Microgram/ Kg/ min produces Renal vasodilatation
  • Dopamine receptor with inhibitory action is D2
Don't Forget to Solve all the previous Year Question asked on DOPAMINE