ISSN:
1432-2072
Keywords:
D1-Receptors
;
Benzazepines
;
Healthy subjects
;
Selective D1-antagonists
;
Side effects
;
Antipsychotics
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Selective dopamine D1-receptor antagonists have been shown to exhibit similar effects in animal models for antipsychotic action as the selective D2 antagonists. NNC 01-0687, a benzazepine with selective and high affinity to the D1-receptor, was well tolerated by healthy subjects allocated to double blind, placebo controlled studies. Complaints of moderate restlessness and drowsiness were reported after administration of 25 mg NNC 01-0687, indicating the dose to be the maximum tolerated single dose. The highest multiple dose level of a daily dose of 45 mg NNC 01-0687 administered t.i.d. for 14 days was assessed as safe and well-tolerated with few reports of adverse events. Some alanine amino-transferase (ALT) elevations appeared in both treatment groups (active and placebo) and no evident influence of NNC 01-0687 on the liver function could be derived. No statistically significant or clinically relevant effects were observed in haematological parameters, urinalyses, blood pressure, heart rate, ECG or plasma levels of prolactin, cortisol or growth hormone. The plasma drug concentration curves indicated a fast absorption with tmax at 0.5–1 h and an apparent elimination half-life of 3–4 h. Both AUC and Cmax appeared to be linearly correlated to the dose, indicating linear pharmacokinetics. With similar Cmax and AUC on day 1 and day 10 no accumulation was observed. When administered just after lunch, the Cmax was reduced by 50–60% and the tmax increased to 3 h, but without change of AUC.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF02246066
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