since people getting a steady blood concentration of l-dopa via a duodopa system have less off times, have to assume dopamine receptors get densensitized by the fluctuation l-dopa, maybe it's just the brain's normal response to high levels of dopamine since our nigral cells are no longer storing dopamine and other areas of the brain are being used to affect our muscles?

keeping in mind less than `10% of l-dopa gets to the brain this doesn't seem like a lot of l-dopa.

that's just a wild guess but you can go back 30 years and read about the "off" problem likely being solved by a long lasting l-dopa, and wonder if DBS therapy has put a damper on companies wanting to develop drugs that extend the "ON", which is why you get only small companies working on it and an IMPAX labs that can't get FDA approval for RYTARY because of unacceptable mfg'ing facility in calif.