L-DOPA and carbidopa in the therapy of Parkinson's disease

 L-DOPA and carbidopa in the therapy of Parkinson's disease

Like the transporters for the catecholamines and serotonin, those for their precursor amino acids are not of very high specificity. This has been exploited in various ways for pharmacotherapy. A very important example is the use of L-DOPA as a pre-drug to substitute dopamine to the brain in patients with Parkinson's disease (Figure 10.18a). Dopamine itself cannot cross the blood brain barrier13. However, L-DOPA is accepted by an amino acid carrier that normally transports aromatic amino acids. It can thus enter the brain and there be decarboxylated to dopamine.

 

Concurrently with its permeation into the brain, howev-er, DOPA will also be decarboxylated in the periphery to dopamine; thus, the overall fraction of DOPA that winds up in the brain is only about 2%. This means that very high dosages will be required for the desired clinical effect, and the periphery would be uselessly troubled with high amounts of dopamine and derived catecholamines. This situation can be greatly improved by the simultaneous ap-plication of an inhibitor of DOPA decarboxylase, called carbidopa (Figure 10.18b). Note that this substance will not cross the blood brain barrier, and therefore not interfere with the (necessary) decarboxylation in the brain.

 

Note that, since dopamine is the precursor of nore-pinephrine and epinephrine, carbidopa will inhibit the syn-thesis of all three catecholamines. One therefore might expect it to reduce blood pressure, but it in animal experi-ments it rather seems to increase it; this has been attributed to the lack of dopamine in the periphery.

Comments

Post a Comment

Popular posts from this blog

Lacerations

  Lacerations   A tear is called laceration. The tear can occur in the vaginal wall or in the perineum or in the cervix. Tears of the perineum are graded according to their severity. Other areas of trauma may be the cervix and extended tears of the vagina.   Causes   ·          Not controlling the head at delivery   ·          Precipitate labour   ·          Big baby   ·          Face to pubis and after coming head of breech   ·          Instrumental delivery   ·          Old scar tissue and face presentation   Type of perineal lacerations   First degree   Involves the vaginal mucous and the skin of the perineum.   Second degree   Involved the deeper layer of perineal muscle   ...
Read more

The origin of cell excitation

Image
  The origin of cell excitation The mechanisms we have discussed above account for the propagation and for the termination of the action potential. However, so far we have relied on external electrodes for its initiation. Under physiological conditions, action potentials can be evoked in various ways. The first, very important means of action potential genera-tion consists in synaptic transmission. A synapse connects a presynaptic cell (always a neuron) to a postsynaptic cell (a neuron or muscle cell). In brief, a synapse works as fol-lows:   1.    Excitation of the presynaptic cell leads to the release of a neurotransmitter substance.   2.    The neurotransmitter binds to a receptor on the postsy-naptic cell, very commonly a ligand-gated channel.   3.    The receptor channel opens and locally depolarizes the membrane.   4.    The local depolarization is picked up by adjacent voltage-gated channels and propagated across th...
Read more

The Normal Puerperium

  THE NORMAL PUERPERIUM At the end of this chapter students will be able to:   ·                   Define peurperium   ·                   State physiological changes during peurperium   ·                   Describe postnatal care given for mother and baby.     Defintion  - Puerperium is period from the expulsion of theplacenta to the time the reproductive organs returns to pregravid state lasts 6 weeks.   Puerperium is characterized by the following features   ·                   The reproductive organs return to the non pregnant state ·            ...
Read more