The drugs in this section are considered together because their major therapeutic application is in treatment of Parkinson’s disease, although some of related antimuscarinic (anticholinergic) drugs included here are also used for other conditions. Parkinson’s disease is named after Dr James Parkinson who originally described four main signs of disease, namely rigidity, tremor, dystonias and dyskinesias (movement disorders). Similar symptoms may also be displayed as unwanted adverse effects of therapy with certain drugs.
The basic cause of disease lies in basal ganglia of brain, particularly striatum and substantia nigra, where normal balance between dopaminergic nerve fibres (those that use dopamine as chemical transmitter) and cholinergic nerve fibres (those that use acetylcholine as transmitter) is lost, because dopaminergic fibres degenerate. As a result cholinergic fibres end up in relative excess. Much of treatment of Parkinson’s disease is based on an attempt to redress balance, and there are several groups of drugs that can be used to this end. These are listed in table 1 below,(below), and discussed below.
Levodopa can pass blood-brain barrier (unlike dopamine), where it is converted into dopamine, and thus acts by topping up CNS dopaminergic system. Levodopa is most usually given with carbidopa or benserazide (dopa-decarboxylase inhibitors), which prevent wasteful peripheral metabolism of levodopa. This allows lower doses of levodopa to be given,which results in fewer adverse effects.
These drugs may augment dopaminergic activity in brain
Bromocriptine, cabergoline, pergolide, ropinirole and similar drugs act as dopamine agonists and so also have effect of increasing dopaminergic activity in brain.
The catechol-O-methyltransferase (COMT) inhibitors work by inhibiting peripheral metabolism of levodopa by COMT. Note that this enzyme is major metabolising enzyme for levodopa when a decarboxylase inhibitor (e
The selective irreversible MAO-B inhibitors enhance dopamine activity by preventing dopamine degradation. These drugs sometimes interact like older non-selective MAOIs, and reader is cross-referred to information under MAOIs when appropriate. Selegiline undergoes rapid first-pass metabolism to produce amfetamine metabolites. A buccal tablet has been developed,which markedly reduces this first-pass metabolism, and is consequently given as a smaller dose.
Benzhexol, orphenadrine, procyclidine and other antimuscarinic (anticholinergic) drugs work by correcting relative cholinergic excess.
The interactions that affect antimuscarinic effects of these drugs are discussed in this section. However, antimuscarinics also affect actions of other drugs (such as centrally-acting anticholinesterases) and these are therefore discussed elsewhere in publication.
Entacapone,Tolcapone
Bromocriptine,Cabergoline, Lisuride, Pergolide
Piribedil,Pramipexole, Quinagolide, Ropinirole, Rotigotine
Rasagiline,Selegiline
Benserazide,Carbidopa
Benzatropine,Biperiden, Bornaprine, Dexetimide, Metixene, Orphenadrine, Procyclidine, Profenamine, Trihexyphenidyl, Tropatepine
| Table 1 Antiparkinsonian drugs | |
| Group | Drugs |
| Dopaminergic drugs | |
| Amino-acid precursor of dopamine | Levodopa |
| Levodopa combined with a peripheral dopa-decarboxylase inhibitor | Co-beneldopa (levodopa + benserazide) Co-careldopa (levodopa + carbidopa) |
| COMT-inhibitors | Entacapone, Tolcapone |
| Dopamine agonists | |
| Ergot derivatives | Bromocriptine, Cabergoline, Lisuride, Pergolide |
| Non-ergot dopamine agonists | Piribedil, Pramipexole, Quinagolide, Ropinirole, Rotigotine |
| Other dopamine agonists | Apomorphine |
| MAO-B inhibitors | Rasagiline, Selegiline |
| Other | Amantadine |
| Other | |
| Peripheral dopa-decarboxylase inhibitors | Benserazide, Carbidopa |
| Antimuscarinics | Benzatropine, Biperiden, Bornaprine, Dexetimide, Metixene, Orphenadrine, Procyclidine, Profenamine, Trihexyphenidyl, Tropatepine |