Off period of Parkinson dz

[MudPhud20XX]

Is the "off" period of Parkinson mainly due to the long-term therapy of PD or is it considered as one of the symptoms of PD? My understanding of off period is basically the immobility. So is "on" period considered as increased dyskinesias?

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[NeuroLAX]

Motor complications in Parkinson's disease can be attributed to long-term therapy. The on-off phenomenon is one such motor complication with motor fluctuations. Generally speaking, "on" refers to when there is good response to medication, and "off" refers to suboptimal therapeutic effect with re-emergence of symptoms. Levodopa-induced dyskinesia is another type of motor complication, typically seen during peak dopamine levels. That's what makes dosing regimens difficult to titrate throughout the day- not too much, not too little.

A more detailed version...

 

[Macaroon_Berry]

From Kaplan - the on period is response to the Anti-Parkinson's drugs mainly Levodopa (increasing dopamine can also lead to hyperkinetic dyskinesias), while the off period is metabolism of the drug and reverting back to the Parkinson's dyskinesias, so when you take another dose you have another on period followed by an off period.

 

[MudPhud20XX]

Motor complications in Parkinson's disease can be attributed to long-term therapy. The on-off phenomenon is one such motor complication with motor fluctuations. Generally speaking, "on" refers to when there is good response to medication, and "off" refers to suboptimal therapeutic effect with re-emergence of symptoms. Levodopa-induced dyskinesia is another type of motor complication, typically seen during peak dopamine levels. That's what makes dosing regimens difficult to titrate throughout the day- not too much, not too little.

A more detailed version...

Thank you for the great explanation. So in order to avoid this on off effect due to the difficulty of managing the dosage of levodopa, selective D2 agonist such as Pramipexole is known to avoid this on and off effect, if that's true, could you explain the mech here? Thank you very much again.

 

[NeuroLAX]

Thank you for the great explanation. So in order to avoid this on off effect due to the difficulty of managing the dosage of levodopa, selective D2 agonist such as Pramipexole is known to avoid this on and off effect, if that's true, could you explain the mech here? Thank you very much again.

That's a difficult question to answer because, like many topics in neuroscience, the mechanisms are still being studied and it's not completely clear what's going on. If you go on pubmed you can read some of the newest papers.

 

[worldbeater]

Also side note, the reason Levodopa/Carbidopa is used as a combination for Parkinson's is the ability of Carbidopa to be processed via the p450 system in the liver and cause the Levodopa to stay in the body for a longer period of time.

 

[seminoma]

Also side note, the reason Levodopa/Carbidopa is used as a combination for Parkinson's is the ability of Carbidopa to be processed via the p450 system in the liver and cause the Levodopa to stay in the body for a longer period of time.

What? Carbidopa is a peripheral decarboxylase inhibitor. What does p450 metabolism have to do with it?

 

[worldbeater]

Sorry your right. I should have said it affects dopa decarboxylase in the liver, not p450.