Sublingual apomorphine: a new pharmacological approach in Parkinson's disease?
Apomorphine, a potent dopamine agonist with mixed D1 and D2 properties, has long been recognized to have antiparkinsonian effect. Its oral administration is limited by both its hepatic first pass metabolism and adverse side effects (nausea, vomiting, azotemia). It is now widely used by subcutaneous route for the treatment of severe "off" periods seen with levodopa treatment. However, the use of penjects can be difficult in some patients with severe tremor or akineto-rigid symptoms during "off" periods. Our group has recently investigated the effect of sublingual administration of apomorphine in patients suffering from Parkinson's disease. Sublingual apomorphine was shown to reduce extrapyramidal symptoms. The main characteristics of the pharmacodynamic effects of sublingual apomorphine in parkinsonians and the relationship between pharmacodynamic and pharmacokinetic effects are discussed. Sublingual apomorphine has the advantage of being easier to administer than subcutaneous injection. For the moment, the long-term use of sublingual apomorphine is limited by two major problems: first, time for dissolution and switch "on" (which is longer than after subcutaneous route) and secondly, the occurrence of local side effects (stomatitis). Further clinical studies using either more efficient (tablets with faster dissolution) and better tolerated sublingual formulations or other dopamine agonists should be carried on before recommending this approach in the treatment of Parkinson's disease.
Montastruc
J L
JL
Laboratoire de Pharmacologie Médicale et Clinique, INSERM U317, Faculté de Médecine, Toulouse, France.
Rascol
O
O
Senard
J M
JM
Houin
G
G
Rascol
A
A
D000286:Administration, Sublingual; D000978:Antiparkinson Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D001058:Apomorphine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018491:Dopamine Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D010865:Pilot Projects
D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D001058:Apomorphine