Neurotransmitters Flashcards
Define neurotransmitters
Endogenous substances that as chemical messengers , used by neurons to communicate
Prior to their release into synaptic cleft, they are stored in secretory vesicles. Called presynaptic vesicles
The neurotransmitters cross the synaptic cleft and binds to specific receptors in the membrane of post-synaptic neuron or cell
Classify the neurotransmitters
According to structure:
Amino acids:
Glutamate
GABA
Aspartate
Glycine
Biogenic amines:
Acetylcholine
Monoamides (catecholamines-indolamines-Histamine)
Neuropeptides:
Opioid peptides
Others:
Nitric oxide
According to functions:
-Excitatory: Glutamate
-Inhibitory: GABA
Excitatory and inhibitory:
Depending on the type of receptors
How are NTs inactivated?
1-Reuptake: Neuron takes NT back up and recycles it for later use
Therapeutic application: SSRI
2-Hydrolysis: Specialized enzymes attack and destroy NT
Therapeutic uses: MOA inhibitors
Discuss glutamate and aspartate neurotransmitters
1-Non-essential, excitatory NTs
2-glutamate is the principle excitatory and removed by reuptake
3-Elevated levels of excitatory amino acid is neurotoxic and cause neuronal death or injury
Discuss GABA
Principal inhibitory NT derived from glutamic acid by glutamic acid decarboxylase and pyridoxal phosphate is needed as coenzyme
It’s level is reduced in brain in vitamin b6 deficiency with signs of convulsions and hyperactivity
What is the (fate-deficiency-agonists) of GABA
Fate:
By the action of GABA transaminase , GABA is transformed into succinate semi aldehyde and the oxidized to succinate to be utilized in Krebs cycle
Deficiency is related to epilepsy and seizures
Agonists: Benzodiazepine and Barbiturates
Discuss Glycine
Major inhibitory NT
Synthesized from serine by serine hydroxy-methyl transferase
Removed by reuptake through high-affinity transporter
Discuss acetylcholine and the disease that affects it
Mostly excitatory effects
Myasthenia gravis:
-A chronic autoimmune neuromuscular disease that causes weakness in skeletal muscles
-Autoantibodies against acetylcholine receptors of neuromuscular junction
-Treatment: Drugs against acetyl choline esterase
Define catecholamines and mention their
-derviative
-site of synthesis
Biologically active amines consisting of catechol (aromatic structure with two hydroxyl groups) linked to an amine.
They are derived from tyrosine
-DA and NE are synthesized in the brain and act as neurotransmitters
-NE as E also synthesized in adrenal medulla
The primary end product in medulla is NE in newborn
With advancing age E is dramatically raised and this depends on cortisol
Explain synthesis of catecholamine and rate limiting enzyme and explain :
-the fate
-Catabolism
1-active reuptake by sympathetic nerve endings
It’s the major fate of circulating catecholamines
2-Catabolism to biologically inactive products:
By monoamine oxidase cause oxidative deamination and inactivation
And catechol-o-methyl-transferase
Causes methylation and inactivation
Dopamine converted to homovinillic acid
E and NE converted to Vanillymandelic acid
What is Parkinson’s disease?
A neurodegenerative movement disorder due to insufficient dopamine production as a result of the idiopathic loss of dopamine producing cells in the brain
Explain the treatment of Parkinson’s diseases
Main aim of drug therapy is to replace the deficiency of dopamine in basal ganglia
Because dopamine does not cross the blood brain barrier it’s immediate precursor (L-dopa and Levi-dopa) which does cross the bloods brain barrier is administrated orally
L-dopa is transported to the brain via large neutral amino acid transporter and it is decarboxylated to dopamine
- A combination of L-dopa and carbidopa has been prescribed for this disease
-Cardidopa is dopa decarboxylase inhibitor
reduces the decarboxylation in peripheral tissues enabling a greater concentration of the precursor to reach the brain
What is the use of &methyl dopa
Used in treatment of hypertension as it can competitively inhibit dopa decarboxylase
Explain pheochromocytoma
-A tumor of cromaffin cells in adrenal medulla
-it is manifested by excessive production of catecholamines —> severe hypertension abd palpitation
-There is much increase in VMA levels
-Treated by methy tyrosine which competes with tyrosine in tyrosine hydroxylase enzyme —> inhibition of catecholamine synthesis
Discus.s the monoamine oxidase inhibitor
In neuron MOAI inactivate the enzyme and thus increased level of NE and seretonin
Responsible for antidepressant action of these drugs
