摘要:

AbstractIn a double‐blind, placebo‐controlled study the pharmacokinetic, encephalotropic, and psychotropic properties of fengabine (FEN)‐a novel GABA receptor agonist–were studied in 15 normal subjects utilizing gas chromatography, quantitative pharmaco‐EEG, and topographical analysis methods as well as psychomeric and psychophysiological techniques. The subjects received randomized and, in weekly intervals, single oral doses of placebo; 200, 400, and 800 mg FEN: as well as 75 mg imipramine (IMI) as reference compound. Blood sampling, EEG recordings, and evaluation of pulse, blood pressure, and side effects were carried out at 0, 1, 2, 4, 6, and 8 hr, with psychometric tests at the same times except the first hour.Pharmacokinetic analyses demonstrated rapid absorption of FEN, with plasma peaks in the second hour, dose‐dependent Cmax, and areas under the plasma concentration time curves. Computer‐assisted spectral analysis of the EEG detected from 17 scalp regions and topographical mapping of the drug‐induced Q‐EEG changes demonstrated significant but subtle central effects of FEN, which resembled in certain aspects the marked CNS effects of 75 mg IMI, such as the increase of theta and concomitant beta‐1 activity in the frontocentral and frontotemporal regions, as well as a decrease of fast alpha activity in the frontocentral and frontotemporal regions, as well as a decrease of fast alpha activity and the centroid over the frontotemporal and centroparietal to occipital regions, respectively, specifically after 800 mg FEN. On the other hand, there was a lack of delt augmentation seen after IMI in the occipitotemporoparietal region, lack of theta increase after the two lower doses of FEN, increase of slow alpha rather than a decrease after IMI, and an augmentation of total power (which declined with increasing doses) rather than an attenuation after IMI.Regional differences were obtained also in regard to dose/treatment‐efficacy and time‐efficacy relations. Both compounds exhibited the peak encephalotropic effect in the second hour and a gentle decline thereafter. Behavioral dose‐ and time‐efficacy relations were only observed in the thymopsyche after FEN. These were characterized by an improvement in mood and affectivity after 400 and 800 mg FEN, respectively, as compared to placebo, while a deterioration occurred after the reference compound. On the other hand, 800 mg FEN also induced sedation, reflected by an increase of drowsiness and decrease of drive, which was observed to a much greater extent after 75 mg IMI. Noopsychic changes occurred only in singular variables. Evaluation of pulse, blood pressure, and side effects demonstrated good tolerability of FEN quite in contrast to IMI. Our findings suggest that the GABAergic compound should be stu

ISSN:0272-4391    

DOI:10.1002/ddr.430110312

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

ISSN:0272-4391    

DOI:10.1002/ddr.430110301

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY