Transdermal delivery of dopaminergic agents

It has been more than 30 years since Calne et al.1 described the symptomatic effects of bromocriptine in patients with Parkinson’s disease. After this pioneering work, bromocriptine was the first dopamine (DA) agonist to be marketed for the treatment of Parkinson’s disease (PD). Since that time, at least eight other DA agonists have become available as antiparkinsonian medications throughout the world, i.e., apomorphine, dihydroergocriptine, cabergoline, lisuride, pergolide, piribedil, pramipexole, and ropinirole.2 Each of these drugs has its own specific pharmacologic specifications, but it has been difficult—except for apomorphine used SC—to demonstrate that these compounds have markedly different therapeutic profiles. The clinical development of any new member of this already large pharmacologic family therefore poses the question of its utility: Do we need another DA agonist? The answer to this question is “Yes, but.” Obviously, the presently marketed DA agonists are far from ideal and do not meet several of the needs of patients with PD. Their symptomatic efficacy is less than that of levodopa; they can induce adverse reactions including nausea, hypotension, somnolence, edema, psychosis, and others; they did not prove to modify the clinical progression of the disease; and they do not improve, and sometimes even exacerbate, some of the most disabling nonmotor PD symptoms such as falls, autonomic dysfunction, or dementia.3 Therefore, we need new agents. But novelty alone is simply inadequate. Novelty must be accompanied by the demonstration that any new agonist will provide some advantage or some innovation compared with the already marketed agents. We are not asking for new “me-too” drugs. There are usually three different ways to demonstrate that a new drug is …