It is then converted to dopamine by dopamine-making neurons that survive in the substantia nigra and nonneuronal cells in the striatum. Patients experience a desensitization phenomenon, gradually losing sensitivity to L-dopa, which works for shorter and shorter increments. This may be attributed to dopamine's ability to promote free radical synthesis, which may help explain why dopamine-making neurons are particularly susceptible to dying from oxidation. L-dopa increases dopamine levels, eases symptoms, and may ironically damage nigral neurons. With more L-dopa usage, more nigral neurons die, leading to gradual ineffectiveness of the compound.
Total desensitization occurs when nigral neuron levels are extremely low.