Direct Dopaminergic Agonists

Ergolines (synthetic ergot derivatives)

- Bromocriptine, Lisuride, Pergolide

Aporphines (related to apomorphine)

- Piribedil

Bromocriptine

Potent agonist on D2, Partial agonist or antagonist on D1 receptors, Improvement in parkinsonian symptoms occurs within ½ -1 hr of an oral dose of bromocriptine; and lasts 6-10 hours. High dose required, expensive and produce intolerable side effects

Side effects of bromocriptine

vomiting, hallucinations, hypotension, nasal stuffiness, conjunctival injunction

Marked fall in BP with the 'first dose' has occurred in some patients with antihypertensives. Used as a supplement to levodopa at end stages: serves to improve control and smoothen 'end of dose' and 'on-off' fluctuations

LISURIDE

D2 and 5-HT agonistic. D1 antagonistic activity. Upto 5 mg/day added to levodopa therapy, improved the clinical rating of patients and reduced 'on off effect

Side effects are similar to bromocriptine, but more somnolence and hallucinations are produced, probably due to its serotonergic action

PERGOLIDE

10times more potent than bromocriptine. Activates D2 and D1 receptors. Clinical efficacy and role in Parkinsonism is similar to bromocriptine, the total 'on' time is increased because of its longer t1/2. Nausea and hypotension are less troublesome

AMANTADINE

Antiviral drug for prophylaxis of influenza A2. Found serendipitously to benefit parkinsonism. Act, more rapidly but has lower efficacy than levodopa, though higher than anticholinergics. About 2/3 patients derive some benefit, tolerance develops over months and efficacy is lost. Appears to act by promoting presynaptic synthesis and release of DA in brain. Action on glutamate receptors through which the striatal dopaminergic system exerts its influence has also been suggested. used in milder cases, or in short courses to supplement submaximal doses of levodopa

Side effects of amantadine

Generally not serious: insomnia, dizziness, confusion, nightmares and rarely hallucinations. A characteristic side effect due to local release of CAs resulting in vasoconstriction is livedo reticularis and edema of ankles. Side effects are accentuated when it is combined with anticholinergics. AMANTREL® 100 mg tab

SELEGILINE (Deprenyl)

Selective MAO-B inhibitor, Intracerebral degradation of DA is retarded. Mild antiparkinsonian action in early cases. Administered with levodopa; prolongs levodopa action, attenuates motor fluctuations and decreases 'wearing off' effect. Adjuvant to levodopa, beneficial in 50-70% patients and permits 20-30% reduction in levodopa dose. Clinical benefits are short lived (6-26 months)

Adverse effects of selegiline

Postural hypotension, nausea, confusion.

Contraindicated in convulsive disorders

Interacts with pethidine

Excitement, hyperthermia, respiratory depression

SELMAX®, SELGIN® 5 mg tab;

Category: Pharmacology Notes