09.06.2 Inactivation by Transport back into the Nerve

An example of a drug that inhibits the inactivation of a neurotransmitter back into a nerve is fluoxetine (Prozac).  Fluoxetine inhibits the inactivation of the neurotransmitter 5-hydroxytryptamine (5-HT), which is useful in the treatment of major depression.  Major depression is depression out of proportion with the cause of the depression.  Major depression is classically characterized by feelings of intense sadness and despair, mental slowing and loss of concentration, pessimistic worry, lack of pleasure, self-deprecation, and agitation or hostility.  Major depression is characterised by physical changes, such as insomnia or hypersomnia (sleeping too much), altered eating patterns, decreased energy and libido, and disruptions of normal circadian rhythms (e.g. hormonal secretion times are altered).

On activation of the tryptaminergic nerve terminal, 5-HT is released and stimulates 5-HT receptors on the postjunctional membrane to have an effect.  5-Hydroxytryptamine (is inactivated by transport back into the neurone on the serotonin transporter (SERT), and this leads to the termination of action of 5-HT.  The short term effect of fluoxetine (Prozac) is to selectively inhibit the SERT transporter, which inhibits the inactivation of 5-HT.  Consequently, there are increased levels of 5-HT in the synapse, which leads to an increased stimulation of receptor, and an increased effect.  Fluoxetine is selective for the SERT transporter, and has little effect on the transport of noradrenaline.  Fluoxetine is one example of a group of drugs known as the selective serotonin reuptake inhibitors (SSRIs).

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