DOPAMINE AND PD Introduction Belongs to the family
DOPAMINE AND PD
Introduction • Belongs to the family of catecholamine's • Dopamine can be further converted into the hormones epinephrine and norepinephrine (also catecholamine’s) • Plays a role in regulation of hormones, motor control and learning • Found in humans, animals- both vertebrates and invertebrates
Production • Produced in the substantia nigra and the ventral tegmental area • It is a neurohormone and is released by the hypothalamus
Dopamine Receptors • Two classes: D 1 -like receptor class - D 1 (locomotion, reward, etc. ) and D 5 (Learning and memory) receptor subtypes Activates adenylyl cyclase which leads to increase in concentration of c. AMP D 2 - like receptor class – D 2 (locomotion, learning, etc. ), D 3 (cognition and emotion) and D 4 (mostly unknown, possibly cognition) receptor subtypes Inhibits adenylyl cyclase leading to decrease in concentration of c. AMP - Have similar signaling properties, however have different signal transduction pathways - They are G protein-coupled receptors, signaling mediated by interaction with GTP- binding proteins
Dopamine Pharmacology • Can be used as an injectable drug • Intropin, Dopastat, Revimine • used in the treatment of severe hypotension, bradycardia (slow heart rate), circulatory shock, or cardiac arrest • Toxicty-LD 50 -59 mg/kg
L-DOPA • Levodopa- dopamine precursor to treat Parkinson’s Disease and dopa-responsive Dystonia • Typically co-administered with an inhibitor of peripheral decarboxylation • Inhibitors of alternative metabolic route for dopamine by catechol-O-methyl transferase are also used • These include entacapone and tolcapone.
Psychostimulants • Cocaine and substituted amphetamines all increase dopamine neuronal activity • These use different mechanisms than L-DOPA • Cocaine- dopamine transporter and norepinephrine transporter blocker
Antipsychotic Drugs • A range of drugs that reduce dopamine activity have been found useful in the treatment of schizophrenia and other disorders • I. E. Valium
Role in Parkinson's Disease • Parkinson's Disease has been related to the loss of dopamine secreting neurons in the midbrain called the substantia nigra. • The projection of dopamine neurons from the substantia nigra pars compacta to the dorsal striatum plays a significant role in the control of motor function and in learning new motor programs. These neurons are especially vulnerable to damage and when a large fraction of them die, the result is PD. • The administration of L-DOPA, the metabolic precursor for dopamine, is a treatment that cannot restore the dopamine cells that have been lost, but causes the remaining cells to produce more dopamine to compensate for what's lost.
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