Monoamine oxidase B inhibitors

Comments · 181 Views

Levodopa and dopamine are metabolised in the brain by monoamine oxidase B (MAO-B) and COMT.

Levodopa and dopamine are metabolised in the brain by monoamine oxidase B (MAO-B) and COMT. Selegiline selectively inhibits MAO-B and prolongs the duration of effect of levodopa. It also provides mild symptomatic benefit when used as monotherapy. The most common significant adverse effect is confusion or delirium. Patients should be warned about the possibility of a tyramine-induced hypertension if a selective monoamine oxidase A inhibitor (e.g. the antidepressant moclobemide) is also prescribed.

 

Catechol-O-methyltransferase (COMT) inhibitors

If dopa decarboxylase is inhibited, peripheral levodopa is predominantly metabolised by catechol-O-methyltransferase (COMT). COMT inhibitors prolong the plasma half-life of levodopa and therefore reduce motor fluctuations. Dopaminergic adverse effects can result, including increased peak-dose dyskinesia and confusion. Class-related adverse effects include urine discoloration, diarrhoea and abdominal pain.

 

Entacapone has a short half-life (90 minutes) and must be taken concurrently with each dose of levodopa. It does not have a central effect as it does not cross the blood-brain barrier. Tolcapone has a longer half-life but has been withdrawn in Australia because of rare severe or fatal hepatic toxicity. It can be obtained under the restricted conditions of the Special Access Scheme.

 

Anticholinergics

Although anticholinergics were the mainstay of treatment prior to the advent of dopaminergic drugs, their current role is limited because of their relative lack of efficacy and the frequent occurrence of unacceptable adverse effects such as memory impairment, confusion and psychosis, dry mouth, difficulty with micturition and constipation. Anticholinergics can occasionally be of benefit when tremor is prominent and poorly responsive to dopaminergic therapy. Withdrawal of long-term therapy with anticholinergics can be difficult and should be done slowly to avoid precipitating a cholinergic crisis.

 

Dopamine agonists

The oral dopamine agonists directly stimulate striatal neurons. They have a longer plasma half-life than levodopa, and thus provide a more continuous dopaminergic stimulation. In the doses tolerated by most patients, they usually do not provide the same degree of motor improvement as levodopa. They do not work if levodopa has failed to benefit the patient. The efficacy of the available dopamine agonists is similar. Equivalent daily doses of bromocriptine, pergolide and cabergoline are 10 mg, 1 mg and 1 mg respectively.

 

The newer agonists are probably better tolerated than bromocriptine, although there have been few comparative studies.1 The long half-life of cabergoline (65 hours) allows a once daily dosage, whereas the shorter half-life of bromocriptine and pergolide can make it easier to tailor therapy. Pramipexole and ropinirole are non-ergoline derived preparations which are not available on the Pharmaceutical Benefits Scheme in Australia but are used extensively overseas.

Comments