1. Treatment of Parkinson’s disease

2. Overview of CNS
Act presynaptically by influencing the production, storage, or termination of action of neurotransmitters.
Other agents may activate or block postsynaptic receptor.

3. Neurotransmission in the CNS
Similar to autonomic nervous system
The circuitry of the CNS is much more complex than the autonomic nervous system
Contains powerful networks of inhibitory neurons that are constantly active
More than 10 neurotransmitters

4. Synaptic potentials
Receptors at most synapses are coupled to ion channels.
Depolarization or hyperpolarization of the postsynaptic membrane, depending on the specific ions that move and the direction

5. Excitatory pathways
Excitatory postsynaptic potential(EPSP) are generated by the following
1. stimulation of an excitatory neuron causes the release of neurotransmitter molecules
2. The influx of Na+ causes a weak depolarization
3. Pass a threshold, and an all-or-none action potential is generated.

6. Inhibitory pathways
Results in a hyperpolarization of the postsynaptic membrane. Inhibitory postsynaptic potentials (IPSP) are
1. releases neurons releases neurotransmitter molecules, such as γ-aminobutyric acid (GABA) or glycine. Increase in the permeability of specific ions, such as, potassium and chloride ions
2. the influx of chloride and efflux of potassium cause a weak hyperpolarization or IPSP that moves the postsynaptic potential away from its firing threshold.

7. Overview of parkinson’s disease
Parkinson's disease (PD) is a progressive disorder of the nervous system. With an annual incidence of approximately 20 new cases per 100,000 people.
PD is generally age-specific; it is estimated that approximately 1% of the population over age 60 has PD.

9. Etiology
Is correlated with a reduction in the activity of inhibitory dopaminergic neurons in the substantia nigra and corpus striatum.

10. Cross-section of the human brain showing the substantia nigra, the region affected by Parkinson's disease

11. Substantia nigra striatum
Fire tonically, rather than in response to specific muscular movements or sensory input.
GABA
dopamine

12. etiology( in summary)
Destruction of cells in the substantia nigra results in the degeneration of neurons responsible for secreting dopamine in the neostriatum.

13. Strategy of treatment
Therapy is aimed at restoring dopamine in the basal ganglia and antogonizing the excitatory effect of cholinergic neurons.

14. Drugs used in PD
levodopa(L-dopa) and carbidopa

15. Mechanism of action Levodopa: replenish the dopamine deficiency.
Dopamine itself does not cross the blood-brain barrier.
Levodopa is readily transported into the CNS and is coverted to dopamine in the brain.
But side effects in the periphery.

16. Carbidopa
A dopamine decarboxylase inhibitor that does not cross the blood-brain barrier
Diminishes the metabolism of levodopa in the GI tract and peripheral tissues

17. Actions
Levodopa decreases the rigidity, tremors, and other symptoms of PD

18. Therapeutic uses
Levodopa in combination with carbidopa is a potent and efficacious

19. Absorption and metabolism
Levodopa has extremely short half-life(1 to 2 hours)
Taken on an empty stomach, typically 45 min before a meal.

20. Adverse effects Peripheral effects: anorexia, nausea, and vomitting
Hypotension

21. CNS effects Visual and auditory hallucinations and dyskinesia
Depression and anxiety

22. Interactions
The vitamin pyridoxine(V6) increases the peripheral breakdown of levodopa and diminishes its effectiveness

23. Bromocriptine Is a dopamine receptor agonist
Produces little response in patients who do not react to levodopa