Currently used DAAs include the “ergot-derived” or “ergoline” drugs bromocriptine, cabergoline, lisuride, and pergolide, with chemical structures based on ergot, a plant alkaloid. The newer, “non-ergot” synthetic DAA, piribedil, pramipexole, and ropinirole – chemically unrelated to ergot – are being promoted vigorously. Side effects Inhibitors,research,lifescience,medical typical of all DAAs (as well as levodopa) include nausea, vomiting, dizziness, and orthostatic hypotension.11,15,18-20 At higher doses, DAAs may induce

confusion, hallucinations, and psychosis, although these usually GDC-0973 mw appear in the advanced stages of the disea.se.21 Sedation and insomnia are other reported side effects of some DAAs, as well as of levodopa, and are probably not associated with any specific agonist. Attention has recently been drawn to somnolence as a possible adverse effect of DAAs (including levodopa). Events of a compelling urge to sleep (so-called “sleep attacks”) have been observed in patients treated with DAAs.22-26 Inhibitors,research,lifescience,medical This is a serious side effect, that, may cause driving accidents. This Inhibitors,research,lifescience,medical needs to be considered and explained

to the patient, particularly if he or she is involved in activity in which the somnolence, even if not excessive, could endanger them or others. Some of the side effects specifically linked to the ergot derivatives include digital or coronary vasospasm, as well as pleuropulmonary and retroperitoneal fibrosis. These are not associated with the Inhibitors,research,lifescience,medical newer and safer non-ergot DAAs piribedil, ropinirole, and pramipexole.27 A transdermal formulation of the experimental D2 selective agonist rotigotine is currently in development.28 It has been found to reduce daily levodopa doses by 30% in a multicenter phase 2b trial in mild-to-severe PD. Apomorphine is the most, potent DAA, and the only one that stimulates effectively both DA D1 and D2 receptors (as does DA itself). However, its therapeutic effect is

hampered by its complex interindividual pharmaco-kinetics and pharmacodynamic variability and its narrow therapeutic range. Apomorphine cannot Inhibitors,research,lifescience,medical be used as an oral drug, but. subcutaneous injections are very helpful, particularly for patients with prolonged “off” the episodes. Continuous delivery of apomorphine subcutancously through a pump is available, but. is technically complex to use and expensive.29 In order to overcome these difficulties, several attempts to create individualized controlled delivery systems for apomorphine are being explored, eg, transdermal iontophoresis and sublingual delivery of the drug. This will be particularly useful for a rapid effect to control fluctuations.30 In a recent study, a carboxymethyl cellulose powder of apomorphine was tested as intranasal sustained-release formulation. These newer delivery systems will hopefully enhance its use as a rescue medication in severe cases.