Central effects of the diuretic, bendrofluazide.

1. Central effects of the diuretic, bendrofluazide (2.5, 5 and 10 mg) were studied in 12 healthy volunteers. Two placebos and an active control drug, oxazepam (15 mg), were included. Single doses were administered double-blind at 10.00 h. The effects of drugs on performance and subjective feelings were assessed before and from 1.5-2.5 and 3.5-4.5 h after ingestion, and recording of the electrical activity of the brain (EEG) and body sway carried out. 2. Performance was assessed using digit symbol substitution, continuous attention, letter cancellation, choice reaction time, finger tapping, immediate and short-term memory, together with critical flicker fusion and two flash fusion. Subjects assessed their mood and well-being on a series of 12 visual analogue scales. The EEG was recorded with eyes open while the subjects carried out a mental arithmetic task, and with eyes closed, when they were required to relax. Body sway was recorded with eyes open and with eyes closed. 3. Bendrofluazide (10 mg) increased the number of errors at letter cancellation and reduced the rate of finger tapping (P < 0.05), while oxazepam increased the number of errors and reduced accuracy at continuous attention (P < 0.01), and increased the number of involuntary rest pauses during tapping (P < 0.05). 4. There were no effects of drugs on subjective assessment of mood. 5. No changes in the electrical activity of the brain were observed with bendrofluazide. In recordings with eyes open, oxazepam reduced delta (0.5-3 Hz), theta (3.5-7 Hz) and alpha 2 (10.5-13 Hz) while increasing beta 1 (13.5-21 Hz) activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Central effects of repeated administration of atenolol and captopril in healthy volunteers.

The central effects of atenolol (50 mg tds) and captopril (50 mg tds) ingested for a period of seven days were studied in ten healthy volunteers. A placebo and two active control drugs, methyldopa (250 mg tds) and oxazepam (10 mg), were included in the design. Oxazepam was ingested on the seventh day only, with a placebo being taken on the preceding six days. On the seventh day, central effects of the drugs were tested at 10.00-11.00 h (session 1), immediately before the subjects' last dose of each drug and at 2.5-3.5 h after the final dose of each drug (1330-1430 h, session 2). Performance was assessed using digit symbol substitution, continuous attention, letter cancellation, choice reaction time, finger tapping, immediate and short-term memory, critical flicker fusion and two flash fusion. Subjects assessed their mood and well-being on a series of 12 visual analogue scales. Recordings of the EEG and body sway were carried out. Neither atenolol nor captopril altered performance at any of the skills tested. There were no effects on subjectively assessed alertness or mood with captopril, while atenolol significantly increased wakefulness in session 2 and when the two sessions were meaned. Similarly, captopril did not modify body sway, while with atenolol there was a significant decrease in activity in the frequency range 1.0-2.75 Hz from session 1 to session 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Central effects of the calcium antagonist, nifedipine.

1. Central effects of the calcium antagonist, nifedipine retard (10, 20 and 40 mg) and nifedipine capsules (10 mg) were studied in 14 healthy male subjects. Two placebos and an active control drug, oxazepam (15 mg), were included. Medication was administered double-blind at 10.00 h. The effects of drugs on performance and subjective feelings were assessed before and from 1.5-2.5 h and 3.5-4.5 h after ingestion, and recordings of the electrical activity of the brain (EEG) and body sway carried out. 2. Performance was assessed using digit symbol substitution, continuous attention, letter cancellation, choice reaction time, finger tapping, immediate and short-term memory, together with critical flicker fusion and two flash fusion. The EEG was recorded with eyes open while the subjects carried out a mental arithmetic task, and with eyes closed, when they were required to relax. Body sway was recorded with eyes open and with eyes closed. Subjects assessed their mood and well-being on a series of 12 visual analogue scales. 3. Nifedipine did not alter performance levels on any of the skills tested, while oxazepam (15 mg) increased the number of errors (P less than 0.01) and reduced accuracy at continuous attention (P less than 0.01). 4. Nifedipine (10 mg) reduced total power of the EEG in the frequency range (0.5-30 Hz), and nifedipine (20 mg) increased total alpha power (7.5-13 Hz) (P less than 0.05). Oxazepam reduced alpha and increased beta 1 power (13.5-21 Hz).(ABSTRACT TRUNCATED AT 250 WORDS)

Central effects of the angiotensin-converting enzyme inhibitor, captopril. II. Electroencephalogram and body sway.

1. Effects of single doses of captopril (12.5, 25 and 50 mg) on the electroencephalogram (EEG) and on body sway were studied in fourteen healthy male subjects. Oxazepam (15 mg), as an active control, and two placebos were included in the study, together with a single dose of atenolol (100 mg). Medication was administered double-blind at 11.00 h, and assessments made before and at 2 and 4 h after drug ingestion. 2. There were no changes in the EEG with captopril. Oxazepam reduced the circadian rise in alpha activity, while atenolol decreased beta power. Delta activity was modified by both oxazepam and atenolol. 3. A reduction in lower frequencies of body sway (0.05-1 Hz) occurred with captopril, while the spectra were unaffected by oxazepam. Atenolol increased (P less than 0.05) activity in the frequency range 0.75-2.75 Hz. 4. These observations suggest that captopril is free of central effects such as sedation that may occur with beta-adrenoceptor antagonists. Reduced body sway with captopril could reflect improved integration of central and peripheral control of posture.

Selective vibration sensing: a new concept for activity-sensing rate-responsive pacing.

A clinically available model of an activity-sensing, rate-responsive pacemaker (Activitrax, Medtronic) utilizes body vibration during exercise as an indicator of the need for a rate increase. Although having the advantage of rapid onset of rate response, this system lacks specificity and the rate response does not closely correlate with the level of exertion. In addition, this pacemaker is susceptible to the effects of extraneous vibration. In this study involving 20 normal subjects fitted with an external Activitrax pacemaker, the rate responses to a variety of exercises were studied and were compared with the corresponding sinus rates. The vibration generated at the level of the pacemaker was also measured by accelerometers in three axes. Only a fair correlation (r = 0.51) was achieved between the pacemaker rate and the sinus rate. The total root mean square value of acceleration in either the anteroposterior or the vertical axes was found to have a better correlation (r = 0.8). As the main accelerations during physical activities were in the lower frequency range (0.1-4 Hz), a low-pass filter was used to reduce the influence of extraneous vibration. Selective sensing of the acceleration level may be usefully implemented in an algorithm for activity pacing.

Central effects of beta-adrenoceptor antagonists. II--Electroencephalogram and body sway.

1. Effects of the beta-adrenoceptor antagonists, propranolol (40, 80 and 160 mg) and atenolol (50 and 100 mg) on the electroencephalogram and on body sway, were studied in 12 healthy male subjects. The study was double-blind, and included two placebos and an active control, oxazepam (15 mg). Medication was ingested at 11.00 h, and assessments were made before, and at 2 h and 4 h after ingestion. 2. All doses of both beta-adrenoceptor antagonists modified the electroencephalogram, and the changes reported were statistically significant at probability levels of less than 5%. The circadian rise in alpha activity was reduced by both beta-adrenoceptor antagonists as well as by oxazepam. Atenolol also decreased beta activity. 3. Body sway was modified by atenolol and oxazepam (P less than 0.05). The increase with oxazepam was most marked in the low frequency component (0.05-2.25 Hz) of the spectrum, while atenolol modified only the component of higher frequency (2.25-4.0 Hz). 4. These observations suggest that propranolol and atenolol have a sedative effect, and that hydrophilic antagonists are unlikely to be free of central activity. The changes in body sway could imply that peripheral mechanisms may be modified at least with atenolol.