N-0923, a novel soluble dopamine D2 agonist in the treatment of parkinsonism.
N-0923, a novel aminotetralin dopamine D2 agonist, was shown to effectively reverse parkinsonian symptoms in nine dopa/agonist-responsive Parkinson's disease patients. The drug was given up to 4.5 hours by continuous intravenous (i.v.) infusion using an i.v. pump. The onset of anti-parkinsonian effect was seen within minutes of the initiation of the infusion and was absent within 90 minutes of cessation of the infusion. The short elimination half-life of N-0923 (90 min) would allow for the rapid initiation of drug effect when necessary and at the same time permit the effect to be terminated quickly if necessary. The drug would be useful in situations where oral medication is not feasible or is associated with erratic absorption. The patients tolerated the drug well. Dose escalation load was limited by nausea and vomiting. It should be noted that the doses were increased until these symptoms occurred, but therapeutic effects were noted well before the side effects occurred. Using a modified Columbia scale, maximum improvement consisted of a 27-95% drop in score. Maximum response was obtained at infusion rates varying from 2-16 microg/kg per hour and at blood levels of 0.11-1.49 microg/mL.
Calabrese
V P
VP
Department of Neurology, Medical College of Virginia, Virginia Commonwealth University, Richmond, USA.
Lloyd
K A
KA
Brancazio
P
P
Cefali
E
E
Martin
P
P
Wall
J
J
Sica
D
D
D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018491:Dopamine Agonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007260:Infusion Pumps; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009460:Neurologic Examination / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy*; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D013764:Tetrahydronaphthalenes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013876:Thiophenes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine