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Carbidopa/Benserazide plus Levodopa for Treatment of Parkinson's Disease Parkinson's disease (PD) is a disease of the brain and central nervous system belonging to a group of conditions called movement disorders. It is characterized by muscle rigidity, resting tremor, a slowing of physical movement (bradykinesia), unwanted random movement of the arms, legs, and head (dyskinesia), random cramping of muscle groups (distonia) and, in extreme cases, a complete loss of physical movement (akinesia). The primary symptoms are the results of decreased stimulation of the motor cortex by the basal ganglia, caused by the insufficient formation and action of dopamine, which is produced in the dopaminergic neurons of the brain located in the substantia nigra. PD is both chronic and progressive. Dopamine is the "gold standard" treatment for PD. But administered orally, it cannot cross the blood/brain barrier. The blood/brain barrier (BBB) is the separation of circulating blood and cerebrospinal fluid (CSF). Endothelial cells restrict the diffusion of microscopic objects (e.g. bacteria) and large or hydrophilic (having a strong affinity for water) molecules into the CSF, while allowing the diffusion of small hydrophobic (water repelling) molecules (O2, hormones, CO2). Cells of the barrier actively transport metabolic products such as glucose across the barrier together with specific proteins. So L-DOPA (levodopa), a drug-related compound found in some food and made from L-Tyrosine, and which is an amino acid naturally occurring in the human body, is administered instead of dopamine. When levodopa is administered orally, it is rapidly converted by to dopamine in extracerebral (outside the brain) tissues so that only a small portion of a given dose is transported unchanged to the brain. Carbidopa is used to inhibit the dopadecarboxylation of peripheral levodopa, making more levodopa available for transport to the brain (benserazide, used as an alternative in some formulations, has a similar effect). When coadministered with levodopa, carbidopa increases plasma levels of levodopa and reduces the amount of levodopa required to produce a given response by about 75%. Carbidopa prolongs the plasma half-life of levodopa from 50 minutes to 1.5 hours and decreases plasma and urinary dopamine. Carbidopa also cannot cross the blood brain barrier, so it inhibits only peripheral dopadecarboxylase. This reduces the side effects caused by dopamine on the periphery, as well as increasing the concentration of levodopa and dopamine in the brain. Dr J F Slattery PhD ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn