Biochemistry_ L3, Neurotransmitter

L3, Neurotransmitter 2 

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▪ Catecholamines:
- Dopamine
- Norepinephrine (NE)
- Epinephrine
▪ Serotonin

Regulation of catecholamine synthesis :
✓Tyrosine hydroxylase :
- it is the key enzyme.
- allosterically inhibited by NE& dopamine( -ve feedback inhibition)

✓Chronic stress:
++Catecholamine synthesis
- Glucocorticoids secreted from the adrenal cortex PNMT to form epinephrine

Dopamine – clinical importance :
The DA theory of schizophrenia (↑DA) is based on the observation that DA antagonists are effective antipsychotic drugs .
Currently , clinical studies are attempting to develop DA antagonists with specific DA receptor subtype efficacy that will most effectively decrease the antipsychotic symptoms without influencing other DA actions , such as movement control.
✓Disorders of Movement Control:
Decreased DA in the substantia nigra and striatum is the critical lesion in Parkinson's disease.
L-DOPA is used to treat this disease's symptoms because it can be converted to
DA in the cells around the degenerated nerve endings to replace the missing
endogenous DA . Other drugs that are effective in treating Parkinson's symptoms are DA agonists , as well as MAO and COMT inhibitors.

Serotonin reuptake inhibitors :

✓dextromethorphan (an antisussive)
✓Tricyclic antidepressants
✓Selective serotonin reuptake inhibitors
(SSRIs) used as antidepressant & anti obesity drugs

Serotonin-Clinical Importance :

✓low levels of 5-HT and metabolites are associated with depression and especially a type of depression that is more likely to lead to suicide.

✓Some antidepressant treatments:
are nonspecific with respect to their relative influence on NE versus 5-HT disposition, thus it has been difficult to know for certain which monoamine is responsible for the treatment effects. More recently selective serotonin reuptake inhibitors(SSRIs) are among the more effective drugs for treatment of depression.