Monoamine Transporter As A Drug Action

1461 words - 6 pages

Neurotransmitters are chemicals; signals are transmitted from neuron to the target cell via a synapse through neurotransmitters. Neurotransmitters are associated in the synaptic vesicles congregated in the presynaptic membrane and are released in the synaptic cleft, In the synaptic cleft they attach to the receptors in the postsynaptic membrane.(1)Monoamine transporters are proteins which are found on nerve terminals of noradrenegenic,serotonergic and dopaminergic neurons. They are also part of sodium dependent transporters and have a key role in terminating the released neurotransmitters action in the synaptic cleft. In addition Transporter proteins are important in assimilating monoaminergic innervations as well as being the main target molecules for numerous amount of antidepressive drugs and substances for abuse. Monoamine transporters consists vesicular monoamine transporters (VMAT) and plasma membrane. Monoamine is carried in to the vesicles by the latter non-selectively and dopamine, nor adrenaline and serotonin is transported into vesicles by Na+/Cl- and selectively former. Monoamine transportation into the cytoplasm is inhibited when antiepileptic drugs for instance SSRI is attached to nor adrenaline transport (NET) or Dopamine transporter (DAT) and serotonin transport (SERT). Thus the monoamine level increases in the synaptic cleft. Monoamine transporters are the site for drug action,(2)Affective disease such as schizophrenia or Parkinson’s disease may be involved due to functional changes in the transporters.

The neurotransmitter transporters are proven to be most important targets for CNS drug discovery,(3)mainly for antidepressant drugs. Antidepressants act as a inhibitors of monoamine transporters. Serotonin selective reuptake inhibitors (SSRIs) are the mostly used. Neurotransmitter transport family was examined by cloning of a rat GABA transporter by Radian and Kanner in 1986 (8). In 1991 pacholyczk et al conducted an experiment to clone the nor epinephrine transporter (9).It was proven that there was a high degree of homology sequence between NE and GABA transporters. Further it was recognized that they are associated with larger gene family (Table1). GABA, GABA/betaine, NE, serotonin, dopamine, glycine, taur- ine and proline were soon identified in further research. These neurotransmitters are dependent on sodium and chloride to activate their function. Between the outside and inside of the cell membrane there are electrochemical gradient of sodium, which gives thermodynamic energy to pump neurotransmitters from low to high concentration in and out of the cell. Chloride ions help in permitting the neurotransmitter and sodium.

(3)

The vesicular neurotransmitter transporters function is to balance the high concentration of amino acid and monoamine neurotransmitter in storage vesicles (3) Serotonin, dopamine, NE, epinephrine and histamine are recognized by vesicular monoamine transporter (VMAT). The monoamine uptake...

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