PMID- 36999711
OWN - NLM
STAT- MEDLINE
DCOM- 20240130
LR  - 20240419
IS  - 1996-3181 (Electronic)
IS  - 1871-5273 (Print)
IS  - 1871-5273 (Linking)
VI  - 23
IP  - 4
DP  - 2024
TI  - Rationale and Development of Tavapadon, a D1/D5-Selective Partial Dopamine 
      Agonist for the Treatment of Parkinson's Disease.
PG  - 476-487
LID - 10.2174/1871527322666230331121028 [doi]
AB  - Currently, available therapeutics for the treatment of Parkinson's disease (PD) 
      fail to provide sustained and predictable relief from motor symptoms without 
      significant risk of adverse events (AEs). While dopaminergic agents, particularly 
      levodopa, may initially provide strong motor control, this efficacy can vary with 
      disease progression. Patients may suffer from motor fluctuations, including 
      sudden and unpredictable drop-offs in efficacy. Dopamine agonists (DAs) are often 
      prescribed during early-stage PD with the expectation they will delay the 
      development of levodopa-associated complications, but currently available DAs are 
      less effective than levodopa for the treatment of motor symptoms. Furthermore, 
      both levodopa and DAs are associated with a significant risk of AEs, many of 
      which can be linked to strong, repeated stimulation of D2/D3 dopamine receptors. 
      Targeting D1/D5 dopamine receptors has been hypothesized to produce strong motor 
      benefits with a reduced risk of D2/D3-related AEs, but the development of 
      D1-selective agonists has been previously hindered by intolerable cardiovascular 
      AEs and poor pharmacokinetic properties. There is therefore an unmet need in PD 
      treatment for therapeutics that provide sustained and predictable efficacy, with 
      strong relief from motor symptoms and reduced risk of AEs. Partial agonism at 
      D1/D5 has shown promise for providing relief from motor symptoms, potentially 
      without the AEs associated with D2/D3-selective DAs and full D1/D5-selective DAs. 
      Tavapadon is a novel oral partial agonist that is highly selective at D1/D5 
      receptors and could meet these criteria. This review summarizes currently 
      available evidence of tavapadon's therapeutic potential for the treatment of 
      early through advanced PD.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.net.
FAU - Bezard, Erwan
AU  - Bezard E
AD  - Universite de Bordeaux, CNRS Institut des Maladies Neurodegeneratives, UMR 5293, 
      Bordeaux, France.
AD  - Motac Neuroscience, Manchester, United Kingdom.
FAU - Gray, David
AU  - Gray D
AD  - Inscopix, Mountain View, CA, USA.
FAU - Kozak, Rouba
AU  - Kozak R
AD  - Novartis, Cambridge, MA, USA.
FAU - Leoni, Matthew
AU  - Leoni M
AD  - Cerevel Therapeutics, Boston, MA, USA.
FAU - Combs, Cari
AU  - Combs C
AD  - Cerevel Therapeutics, Boston, MA, USA.
FAU - Duvvuri, Sridhar
AU  - Duvvuri S
AD  - Cerevel Therapeutics, Boston, MA, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United Arab Emirates
TA  - CNS Neurol Disord Drug Targets
JT  - CNS & neurological disorders drug targets
JID - 101269155
RN  - 0 (Dopamine Agonists)
RN  - 46627O600J (Levodopa)
RN  - 0 (Dopamine Agents)
RN  - 0 (Receptors, Dopamine D2)
RN  - 0 (Receptors, Dopamine D1)
RN  - 0 (Antiparkinson Agents)
SB  - IM
MH  - Humans
MH  - *Dopamine Agonists/therapeutic use
MH  - *Parkinson Disease/drug therapy
MH  - Levodopa/therapeutic use
MH  - Dopamine Agents/therapeutic use
MH  - Receptors, Dopamine D2
MH  - Receptors, Dopamine D1
MH  - Antiparkinson Agents/therapeutic use
PMC - PMC10909821
OTO - NOTNLM
OT  - D1 agonist
OT  - D1/D5 partial dopamine agonist
OT  - Dopamine receptors
OT  - Parkinson's disease
OT  - direct pathway
OT  - indirect pathway
OT  - motor symptoms
OT  - tavapadon.
COIS- EB is a director and a shareholder of Motac Neuroscience, Ltd. RK is a current 
      employee of Novartis and owns stock options in the company. DG is a former 
      employee of Cerevel Therapeutics. SD, ML, and CC are employees of Cerevel 
      Therapeutics and may hold stock and stock options in the company.
EDAT- 2023/04/01 06:00
MHDA- 2024/01/30 12:43
PMCR- 2024/03/04
CRDT- 2023/03/31 07:53
PHST- 2022/10/21 00:00 [received]
PHST- 2023/02/08 00:00 [revised]
PHST- 2023/02/09 00:00 [accepted]
PHST- 2024/01/30 12:43 [medline]
PHST- 2023/04/01 06:00 [pubmed]
PHST- 2023/03/31 07:53 [entrez]
PHST- 2024/03/04 00:00 [pmc-release]
AID - CNSNDDT-EPUB-130629 [pii]
AID - CNSNDDT-23-476 [pii]
AID - 10.2174/1871527322666230331121028 [doi]
PST - ppublish
SO  - CNS Neurol Disord Drug Targets. 2024;23(4):476-487. doi: 
      10.2174/1871527322666230331121028.