New Drug may Offer Better Symptom Relief and Limit Progression of Parkinsons Disease

New Drug may Offer Better Symptom Relief and Limit Progression of Parkinson's Disease

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Highlights:
  • Parkinson's disease (PD) is neuro degenerative disorder which leads to movement associated problems.
  • Slow movement is a common side effect to currently available PD drugs including agonists.
  • New drug compound, D-512, shows higher efficiency in treatment of early stage PD when compared to regularly administered ropinirole.
A new drug compound, D-512, may be able to limit the progression of Parkinson's and also relieve its symptoms when compared to the other currently available drugs. Researchers at Binghamton University have done a comparative study on rats to evaluate the efficacy of ropinirole and D-512 in the management of PD symptoms. The study was published in The British Journal of Pharmacology.
New Drug may Offer Better Symptom Relief and Limit Progression of Parkinson's Disease

Parkinson's Disease and its Treatment:

Parkinson's disease (PD) is caused due to the depletion of neurons in the part of the brain called the substantia nigra. This part of the brain is associated with control of movement. When the neurons here die, so is the chemical they produce, called dopamine. Loss of dopamine leads to loss of movement.

PD involves the progressive loss of dopamine neurons in the substantia nigra, leading to motor symptoms including:
  • Akinesia (Lack Of Movement) Or Bradykinesia (Slow Movement),
  • Resting Tremor
  • Rigidity
  • Postural Instability
There is not one known definite cause for PD, and therefore the disease may not be cured, however, the symptoms can be managed. The commonly used drugs called anti-parkinsonian drugs are used to treat PD like symptoms.

Dopamine cannot cross the blood-brain barrier, and hence externally providing dopamine as a treatment is not possible. However, precursors to dopamine are used as drugs which change into dopamine in the brain. Another group of frequently administered drugs are dopamine agonists that mimic dopamine effects in the brain. Dopamine agonists include pramipexole (Mirapex), ropinirole (Requip), among others.

These drugs have a wide range of side effects including hallucinations and behavioral problems. With long term usage of these drugs, bradykinesia or slow movement is observed in PD patients.

The New Candidate Drug: D-512

To study the anti-parkinsonian properties of the clinically employed ropinirole and the novel D-512, the research team, parkinsonism was simulated in mice and the efficiency of both drug compounds in treating the same were studied. The ability of each drug to stimulate spontaneous motor activity and reverse parkinsonian akinesia was studied.

Highlights of The New Drug Compound:
  • High affinity D2/3 receptor agonist and therefore able to attach and mimic effects of dopamine effectively.
  • Has antioxidant and neuro-protective properties.
  • May have fewer side effects than the currently used medications.
  • Has longer duration of action than ropinirole, although both provoked impaired movements. Anti-parkinsonian effects of ropinirole subsided in 2 hours, but that of D-512 lasted for at least 4 hours.
  • D-512 was able to reverse forelimb akinesia (lack of movement)
  • Rotational behavior, a marker of anti-PD efficacy was greater for D-512 than ropinirole.
  • Blood plasma and brain uptake of D-512 was greater than ropinirole.
"A major issue for Parkinson's disease patients is the need to take multiple medications, multiple times per day. So we were quite astounded to discover that our new compound, D-512, was superior to the widely-used drug, ropinirole, in terms of maximal symptom relief and duration of action," said Lidenbach, first author of the study.

References:
  1. Lindenbach, D., Das, B., Conti, M. M., Meadows, S. M., Dutta, A. K., & Bishop, C. (2017). D-512, a novel dopamine D2 / D3 receptor agonist, demonstrates superior anti-parkinsonian efficacy over ropinirole in parkinsonian rats. British Journal of Pharmacology. doi:10.1111/bph.13937
  2. New drug may treat and limit progression of Parkinson's disease - (https:www.eurekalert.org/pub_releases/2017-07/bu-ndm073117.php)
  3. Parkinson's disease - (http://www.mayoclinic.org/diseases-conditions/parkinsons-disease/basics/treatment/con-20028488)
Source: Medindia

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