Piribedil

Piribedil is an antiparkinsonian agent and piperazine derivative which acts as a D₂ and D₃ receptor agonist. It also has α₂-adrenergic antagonist properties.^[2][3]

Piribedil

Clinical data
Trade names	Pronoran, Trivastal Retard, Trastal, Trivastan, Clarium, others
AHFS/Drugs.com	International Drug Names
Routes of administration	By mouth
ATC code	N04BC08 (WHO)
Legal status
Legal status	EU: Rx-only[1] In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	10% (peak at 1 hour) [citation needed]
Protein binding	70–80% [citation needed]
Metabolism	extensive liver [citation needed]
Elimination half-life	1.7–6.9 hours [citation needed]
Excretion	Kidney (68%) and bile duct (25%) [citation needed]
Identifiers
IUPAC name 2-[4-(benzo[1,3]dioxol-5-ylmethyl)piperazin-1-yl]pyrimidine
CAS Number	3605-01-4 Y
PubChem CID	4850
IUPHAR/BPS	49
ChemSpider	4684 N
UNII	DO22K1PRDJ
KEGG	D07305 Y
ChEMBL	ChEMBL1371770 N
CompTox Dashboard (EPA)	DTXSID9045188
ECHA InfoCard	100.020.695
Chemical and physical data
Formula	C16H18N4O2
Molar mass	298.346 g·mol−1
3D model (JSmol)	Interactive image
SMILES C1CN(CCN1CC2=CC3=C(C=C2)OCO3)C4=NC=CC=N4
InChI InChI=1S/C16H18N4O2/c1-4-17-16(18-5-1)20-8-6-19(7-9-20)11-13-2-3-14-15(10-13)22-12-21-14/h1-5,10H,6-9,11-12H2 N Key:OQDPVLVUJFGPGQ-UHFFFAOYSA-N N
NY (what is this?)  (verify)

Medical uses

• Treatment of Parkinson's disease (PD), either as monotherapy (without levodopa) or in combination with L-DOPA therapy, in the early stages of the disease as well as in the advanced ones^{[citation needed]}
• Treatment of pathological cognitive deficits in the elderly (impaired attention, motivation, memory, etc.)^{[citation needed]}
• Treatment of dizziness in the young patients^{[citation needed]}
• Treatment of retinal ischemic manifestations^{[citation needed]}
• Adjunctive treatment of intermittent claudication due to peripheral vascular disease (PVD) of the lower limbs (stage 2)^{[citation needed]}
• Adjunctive treatment of anhedonia, apathy and treatment-resistant depression in unipolar and bipolar depressives (off-label)^{[citation needed]}
• Treatment of gait disorders associated with Parkinson's disease (no related cause) and other forms of parkinsonism^{[citation needed]}

Other uses

The drug has been shown to enhance working memory capacities in normal aging adults.^[4]

In age-related memory impairment, it has a positive effect on psychophysiological state of elderly people, improving memory and attention and increasing the velocity of psychomotor reactions and lability of nervous processes.^[5]

It enhances cognitive skill learning in healthy older adults.^[6]

It showed a positive effect in restless legs syndrome.^[7]

Side effects

• Minor gastrointestinal upset (nausea, vomiting, flatulence, etc.) in predisposed individuals, or when taken between meals: adjust dosage individually, and/or add domperidone^{[citation needed]}
• Orthostatic hypotension or drowsiness may occur, particularly in predisposed individuals (underlying condition or causative illness)^{[citation needed]}
• Mild dizziness, confusion and feeling "drunk" also may occur^{[citation needed]}

As with other dopamine agonists (like pramipexole and ropinirole), compulsive behavior like pathological gambling, overeating, excessive shopping, increased libido, sexual and/or other intense urges, may develop.^[8][9]

Another rare side effect of piribedil is excessive daytime sleepiness and unintended sleep episodes.^[9][10]

Overdose

At very high doses, piribedil has an emetic action on the chemoreceptor trigger zone (CTZ). Tablets will thus be rapidly rejected, which explains why no data are currently available concerning the risk of overdosage.^{[medical citation needed]}

Interactions

Dopamine antagonists reduce the effect of piribedil.^{[medical citation needed]}

Pharmacology

Pharmacodynamics

• Dopamine receptor agonist, selective for subtypes D₂ and D₃^{[citation needed]}
• Dopamine receptor antagonist, selective for subtypes D₄.^[11][12][13]
• Adrenergic receptor antagonist, subtypes α_2A and α_2C.^[14]
• Lack of affinity to serotonin receptor 5-HT_2B.^[14]