Selective plasma hydrolysis of glucocorticoid gamma-lactones and cyclic carbonates by the enzyme paraoxonase: an ideal plasma inactivation mechanism.
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Aryldialkylphosphatase↗
Biomedical subjects
R J Stubbs
Publications and source records attributed to R J Stubbs.
Altering the temporal distribution of energy intake with isoenergetically dense foods given as snacks does not affect total daily energy intake in normal-weight men.
The objectives of the present study were to examine the effects of (1) ingesting mandatory snacks v. no snacks and (2) the composition of isoenergetically-dense snacks high in protein, fat or carbohydrate, on food intake and energy intake (EI) in eight men with ad libitum access to a diet of fixed composition. Subjects were each studied four times in a 9 d protocol per treatment. On days 1-2, subjects were given a medium-fat maintenance diet estimated at 1.6 x resting metabolic rate (RMR). On days 3-9, subjects consumed three mandatory isoenergetic, isoenergetically dense (380 kJ/100 g) snacks at fixed time intervals (11.30, 15.30 and 19.30 hours). Total snack intake comprised 30% of the subjects' estimated daily energy requirements. The treatments were high protein (HP), high carbohydrate (HC), high fat (HF) and no snack (NS). The order was randomized across subjects in a counterbalanced, Latin-square design. During the remainder of the day, subjects had ad libitum (meal size and frequency) access to a covertly manipulated medium-fat diet of fixed composition (fat:carbohydrate:protein, 40:47:13 by energy), energy density 550 kJ/100 g. All foods eaten were investigator-weighed before ingestion and left-overs were weighed after ingestion. Subjective hunger and satiety feelings were tracked hourly during waking hours using visual analogue scales. Ad libitum EI amounted to 13.9 MJ/d on the NS treatment compared with 11.7, 11.7 and 12.2 MJ/d on the HP, HC and HF diets respectively (F(3,21) 5.35; P = 0.007, SED 0.66). Total EI values were not significantly different at 14.6, 14.5, 15.0 and 14.2 MJ/d respectively. Snack composition did not differentially affect total daily food intake or EI. Average daily hunger was unaffected by the composition of the snacks. Only at 12.00 hours did subjects feel significantly more hungry during the NS condition, relative to the other dietary treatments (F(3,18) 4.42; P = 0.017). Body weight was unaffected by dietary treatment. In conclusion, snacking per se led to compensatory adjustments in feeding behaviour in lean men. Snack composition (with energy density controlled) did not affect the amount eaten of a diet of fixed composition. Results may differ in real life where subjects can alter both composition and amount of food they eat and energy density is not controlled.
Adult↗
Differences in fat, carbohydrate, and protein metabolism between lean and obese subjects undergoing total starvation.
Despite extensive experimental studies on total starvation, many of the findings relating to protein, fat (plus ketone body), and carbohydrate metabolism remain confusing, although they become more consistent when considered in relation to the degree of initial obesity. During prolonged starvation, protein loss and percent energy derived from protein oxidation are 2- to 3-fold less in the obese than in the lean; percent urine N excreted as urea is 2-fold less in the obese; and the contribution of protein to net glucose production is only about half in the obese compared to lean subjects. During short-term starvation (first few days) the following differences are reported: hyperketonaemia is typically 2-fold greater in lean subjects, but associated with a 2-fold lower uptake of ketone bodies by forearm muscle; glucose tolerance becomes impaired more in lean subjects; and both protein turnover and leucine oxidation increase in the lean, but may show no significant change in the obese. It is no longer acceptable to describe the metabolic response to starvation as a single typical response. The differences between lean and obese subjects have important physiological implications, some of which are of obvious relevance to survival.
Blood Glucose↗
Observations in energy and macronutrient intake during prolonged bed-rest in a head-down tilt position.
OBJECTIVE: to report observations in energy and macronutrient intakes, and body weight during prolonged bed-rest in a head down tilt (HDT) position. DESIGN: open study, each subject was his own control, and was studied during 14 days of baseline, 42 days of -6 degrees HDT bed-rest, and 12 days of recovery. SUBJECTS: eight healthy young man were recruited, one dropped out. METHODS: energy and macronutrient content of the diet were calculated from weighed amounts of food consumed and French food composition tables. RESULTS: body weight declined during HDT (74.0+/-3.2 to 71.8+/-3.2 kg, P<< 0.001) and increased during recovery (72.7+/-3.2 kg, P<< 0. 001). Energy intake decreased during HDT (by 17% after 4-5 weeks) and increased during recovery but remained lower than during baseline (P<< 0.001). During HDT fat intake, expressed by a percentage of energy, decreased (P<< 0.01) while carbohydrate increased (P= 0.04); protein intake did not change (P= 0.08). The reverse trends were observed during recovery. CONCLUSIONS: the present study reports a spontaneous reduction in energy and relative fat intake during prolonged HDT bed rest. We believe that these findings have implications for the clinical setting.
Adult↗
A capillary gas chromatographic assay with nitrogen phosphorus detection for the quantification of topiramate in human plasma, urine and whole blood.
An accurate and robust method involving liquid liquid extraction and capillary gas chromatographic (GC) assay with nitrogen phosphorus detection (NPD) was developed and validated for the quantitative determination of topiramate [2,3:4,5-bis-O-(-1-methylethylidene)-beta-D-fructopyranose sulfamate], Topamax, an anticonvulsant drug, in human plasma, urine, and whole blood. The galactopyranose analog of topiramate was used as the internal standard. A DB-5, fused silica capillary column (J&W Scientific, Folsom, CA) was used, yielding typical retention times of 4.95 min for topiramate and 5.32 min for the internal standard in human plasma. The assay involved organic extraction with methyl t-butyl ether (MTBE) from base, a back extraction into acid and a second extraction in MTBE. The organic solvent was evaporated, and the residue was redissolved and injected for analysis. The standard curve was validated from 0.5 to 50 microg/ml(-1) for human plasma and whole blood, and from 1.0 to 50 microg/ml(-1) for urine. Peak area ratios of drug to internal standard were determined and used to construct a standard curve. The resulting chromatograms showed no endogenous interfering peaks with the respective blank human fluids. Chromatograms corresponding to topiramate and the internal standard produced sharp peaks that were well resolved. This assay showed precision and accuracy of < or = 5%. Two minor human metabolites of topiramate did not interfere with the assay. This assay was successfully applied to determine the pharmacokinetics of topiramate during the development of this drug.
Anticonvulsants↗
Description and evaluation of an experimental model to examine changes in selection between high-protein, high-carbohydrate and high-fat foods in humans.
OBJECTIVE: To develop and test an experimental model designed to detect changes in selection between foods individually enriched in protein, carbohydrate and fat in human subjects. DESIGN: Randomised counterbalanced (Latin square) design. SETTING: The metabolic suite at the Rowett Research Institute's Human Nutrition Unit. SUBJECTS: 16 normal-weight men (mean BMI = 23.5). INTERVENTIONS: Subjects were each studied 4 times in a 2-day protocol. On day 1 subjects received a fixed maintenance diet; on day 2 they received a mandatory intake as breakfast (08.30) plus a drink at 10.30. This comprised 80% of resting energy requirements as high-protein (HP), high-carbohydrate (HC) or high-fat (HF) foods (60% of energy in each case) or an equal mixture (M) of macronutrients, 33% by energy. All mandatory treatments contained the same energy content and density. From 12.30 onwards, subjects had ad libitum access to a counter-balanced selection of three groups of familiar foods (10 HP, 10 HC and 10 HF; 30 foods in total). Most energy in each food was derived from one macronutrient (approximately 60%), the remainder being equally split between the other two macronutrients. RESULTS: Subjects were significantly less hungry before lunch on the HP and M (33% protein) treatments (F3.44 = 7.35; P < 0.001). At lunch, they ate more energy after the HF treatment than after any of the other treatment (F1,38 = 9.00; P = 0.005). This was largely in the form of fat and protein, and to a lesser extent carbohydrate. Subsequent energy intake (EI) were lower on the HF treatment, largely through selection of less fat in the afternoon (F1.42 = 6.90; P=0.012). Daily EIs were similar across treatments. CONCLUSION: This design appears sensitive meal-to-meal to changes in both nutrient and EIs.
Adult↗
High and low carbohydrate and fat intakes: limits imposed by appetite and palatability and their implications for energy balance.
This report examines several issues concerning the effects of dietary fats and carbohydrates (CHOs) on body weight and the limits set on the intake of these nutrients by factors influencing appetite control: (i) the physiological relationship between feeding behaviour (FB) and body weight; (ii) the distribution of nutrients in Western foods and the implications this may have for FB; (iii) the contribution of nutrients in the diet, to total EI under both extreme and typical Western conditions; (iv) the known effects that fats, CHOs and dietary energy density (ED) exert on appetite and energy balance (EB); (v) the potential role of sensory factors in promoting or limiting fat, CHO and energy intakes (EI) in modern human populations Population studies and large surveys have identified individuals with wide ranges of fat and CHO intakes. Intakes of fat can vary from an average of 180 g/day to 25 g/day in a representative sample. But on individual days fat intake can rise to well over 200 g according to a selection of high fat foods. In a single meal, people can consume an amount of fat greater than the population daily average. From this analysis it can be deduced that the appetite control mechanism will permit the consumption of large amounts of fat (if an abundance of high fat foods exist in the food supply). Except for specific physiological circumstances (e.g. endurance explorers) where there is an urgent need for EIs, in the face of decreasing body weight, it is unlikely that the body will generate a specific drive for fat. Because CHO foods have a lower ED than fat foods (on average) and because of their greater satiating capacity, the free intake of high CHO foods is likely to be self-limiting (at lower EIs than those generated by fatty foods). This does not mean that excess EIs are impossible when people feed ad libitum on high CHO diets.
Appetite↗
Determination of 2-chlorodeoxyadenosine (cladribine, 2-CdA) in human plasma by liquid chromatography-atmospheric pressure chemical ionization mass spectrometry.
A sensitive and specific assay based on combined liquid chromatography mass spectrometry (LCMS) has been developed and validated for the quantification of 2-chlorodeoxyadenosine (cladribine, 2-CdA) in human plasma. Sample preparation consisted of an extraction with ethyl acetate under basic conditions. The organic solvent was evaporated and the residue re-dissolved for analysis. The extracts were chromatographed on a base deactivated C-8 column interfaced via the heated nebulizer probe to a corona discharge chemical ionization source. The mass spectrometer was operated in the positive ion tandem mode. Typical retention times were 1.5 and 2.0 min for 2-CdA and a fluorinated analog internal standard (IS), respectively. The standard curve was linear from 0.1 to 20 ng ml-1 using a 1.0 ml sample volume. The resulting chromatograms produced sharp peaks for 2-CdA and the IS and showed no endogenous peaks from blank plasma. Peak area ratios of 2-CdA to IS were used for standard curve regression analysis. This assay procedure gave interday mean accuracy results for the standards and quality controls that were within 4.9% of target concentrations and interday precision results (RSDs) that were less than 5.3%.
Antineoplastic Agents↗
Breakfasts high in monoglyceride or triglyceride: no differential effect on appetite or energy intake.
OBJECTIVE: To test whether isoenergetic isoenergetically-dense doses of dietary 1-monoglyceride or triglyceride differentially influence appetite and meal-to-meal energy intake in man. DESIGN: Six men and six women were each studied twice in a 2 d protocol. On day 1 (maintenance day) they were fed a medium fat (MF) maintenance diet (MF: 40% fat, 47% carbohydrate and 13% protein by energy) calculated at 1.6 x resting metabolic rate (RMR). On day 2 (manipulation day) at 08.30 h subjects consumed a high-fat breakfast designed to contain 80-85% of RMR, composition 10% protein, 56% fat and 34% carbohydrate by energy, with 65% of energy for fat derived as either 1-monoglyceride or triglyceride. Food and energy intake were monitored at lunch (given at 12.30pm) and throughout the remainder of the day. During this time subjects had ad libitum access to isoenergetic, isoenergetically dense MF (40:47:13) foods (550kJ/100g), until 22.30pm). Subjective hunger and satiety were tracked hourly, during waking hours. RESULTS: There was no significant effect of fat type on food or energy intake at lunch or during the ad libitum period. There was no diet effect on subjective hunger (F(1,10)0.00; P= 0.975) in the inter-meal periods of morning or afternoon, nor during the whole day. Subjects found both diets to be similarly pleasant (F(1,61)0.84;P= 0.364). Men and women responded similarly, except that men ate more on all occasions than women. CONCLUSIONS: This study suggests that when a large dose of l-monoglyceride or triglyceride is incorporated into a breakfast meal, it behaves in a manner that is very similar to triglyceride in terms of the effects on hunger, appetite or feeding behaviour.
Adult↗
Overfeeding fat as monoglyceride or triglyceride: effect on appetite, nutrient balance and the subsequent day's energy intake.
OBJECTIVE: To examine the effect of overfeeding isoenergetic diets enriched in 1-monoglyceride or triglyceride on nutrient oxidation and appetite throughout the day that it was given and the subsequent day's food and energy intake. DESIGN: Six men [mean (s.d.) weight; 76.89 (7.00) kg, height; 1.77 (0.05) m, age; 26.4 (6.0) y], were each studied twice in a 3 d protocol. On day 1 (maintenance day) they were fed a medium fat (MF) maintenance diet (MF: 40% fat, 47% carbohydrate and 13% protein by energy) calculated at 1.6 x resting metabolic rate (RMR). Subjects entered the calorimeter at 06.30 on day 2 for 49.5 h. On day 2 (manipulation day) subjects consumed a MF diet at 1.6 x RMR with an additional 0.45 x RMR as either 1-monoglyceride or triglyceride. On day 3 (outcome day), subjects had ad libitum access to isoenergetic, isoenergetically dense MF (40 :47: 13, 550 kJ/ 100 g) foods. Subjective hunger and satiety were tracked hourly, during waking hours throughout days 1-3. RESULTS: There was no significant effect of diet on nutrient oxidation or balance either during day 2 (manipulation day) or day 3 (outcome day), fat oxidation was similar on both diets. Subjective hunger was not affected by diet on either day with mean values of 34.3 and 35.0 mm (SED 5.2) on manipulation day (day 2) and outcome day (day 3), 35.3 and 40.8 mm (SED 5.2) on the 1 -monoglyceride or triglyceride diets respectively. Day 3 food and energy intake were unaffected by the previous day's dietary treatment, with mean intakes of 15.9 and 15.6 MJ (SED 1.07) on the 1-monoglyceride or triglyceride treatments, respectively. CONCLUSIONS: This study suggests that when 1-monoglyceride is covertly incorporated into a diet at unusually high levels, it behaves in a manner that is very similar to triglyceride, in its effects on appetite, feeding behaviour and net nutrient balance.
Adult↗
Comparison of the traditional paper visual analogue scale questionnaire with an Apple Newton electronic appetite rating system (EARS) in free living subjects feeding ad libitum.
OBJECTIVE: Assessing the value of a newly developed electronic visual analogue scale questionnaire (Apple Newton Message Pad) with the traditional paper method for appetite rating. DESIGN: In a random, crossover design, subjects completed both electronic and paper questionnaires to compare results obtained by the two methods; individual methods were completed consecutively to assess test-retest reliability; preference was established using a questionnaire. SETTING/SUBJECTS: Healthy, free-living adults were studied for comparison of methods (n = 12), test-retest reliability (n = 8) and preference (n = 13). INTERVENTION: Visual analogue scales were completed each waking hour to assess appetite. Preference was assessed after both methods were completed. RESULTS: There was no significant difference in the hourly results obtained by the paper and electronic methods for 'desire to eat', 'how much can you eat now', 'urge to eat' and 'preoccupation with thoughts of food'. Small differences in 'hunger' and 'fullness' ratings were noted (approximately 5% mean difference between methods, P < 0.05), but patterns of change and sensitivity for these and all other parameters remained similar for both methods across the visual analogue scale. Test-retest reliability demonstrated was similar for both methods. Seven (54%) subjects preferred to use the paper questionnaire, five (38%) the electronic method and one (8%) had no preference. CONCLUSIONS: The electronic Apple Newton questionnaire is as sensitive and reliable as the paper method, has the advantage that it automatically records the time of data acquisition and data collection and processing are more efficient for the researcher. The two methods should not be used interchangeably.
Adult↗
Covert manipulation of energy density of high carbohydrate diets in 'pseudo free-living' humans.
OBJECTIVE: This study examined the effects of varying the energy density (ED) of high carbohydrate (HC) diets on food and energy intake (EI), subjective hunger and body weight in humans. DESIGN: Randomised cross-over design. Subjects were each studied twice during 14 d, throughout which they had ad libitum access to one of two covertly-manipulated diets. SUBJECTS AND METHODS: Six healthy men (mean age (s.d.)=32.17 y s.d. (5.26 y), mean weight=69.74 kg s.d. (2.75 kg), mean height=1.76 m s.d. (0.05 m), body mass index (BMI)=22.57 (2.2) kg/m2) were studied. The fat, carbohydrate (CHO) and protein content (as % energy) and ED of each diet were 21:66:13% and 357 kJ/100 g, (low-energy density (LED)) or 22:66:12% and 629 kJ/100 g (high-energy density (HED)). A medium fat diet was provided at maintenance (1.6 x BMR, MF for 2 d) before each ad libitum period. Subjects could alter the amount, but not the composition of foods eaten. RESULTS: Mean EI was 8.67 and 14.82 MJ/d on the LED and HED diets, respectively. Subjects felt significantly more hungry on the LED diet, than on the HED diet (F(1,160)38.28; P < 0.001) and found the diets to be similarly pleasant (72.72 mm vs 71.54 mm (F(1,392)0.31; P = 0.579)). Mean body weight decreased on the LED diet at a rate of 0.1 kg/d and increased at 0.06 kg/d on the HED diet (F(1,131)86.60; P < 0.001), giving total weight changes of -1.41 kg and +0.84 kg, respectively, both of which were significantly different from zero (P < 0.01). CONCLUSION: Excess EI is possible on HC, HED diets, at least under conditions where diet selection is precluded. Comparison of these results with previous studies, which altered ED using fat, suggests that CHO may be a better cue for hunger than fat.
Adult↗
The effect of covertly manipulating the energy density of mixed diets on ad libitum food intake in 'pseudo free-living' humans.
OBJECTIVE: This study examined the effects of covert alterations in the energy density (ED) of mixed, medium fat (MF) diets on ad libitum food and energy intake (EI), subjective hunger and body weight in humans. DESIGN: Randomised cross-over design. Subjects were each studied three times (factorial design), during 14d, throughout which they had ad libitum access to one of three covertly-manipulated MF diets. SUBJECTS: Six healthy men, mean age (s.e.m.) = 30.0 y (12.76 y), mean weight = 71.67 kg (19.80 kg); mean height = 1.79 m (0.22 m), body mass index (BMI) = 22.36 (2.60) kg/m2, were studied. The fat, carbohydrate (CHO) and protein in each diet (as a proportion of the total energy) and energy density (ED) were, low-ED (LED), 38:49:13%; 373 kJ/100 g; medium-ED (MED), 40:47:13%; 549 kJ/100 g; high-ED (HED), 39:48:13%; 737 kJ/100 g. Subjects could alter the amount but not the composition of foods eaten. They were resident in (but not confined to) a metabolic suite throughout the study. RESULTS: Solid food intake decreased as ED increased, giving mean values of 2.84, 2.51 and 2.31 kg/d, respectively. This was insufficient to defend energy balance, since energy intake increased with increasing ED (F(2,10) 16.08; P < 0.001) giving mean intakes of 10.12, 12.80 and 16.17 MJ/d, respectively. Rated pleasantness of food (measured on visual analogue scales) was not significantly different between diets nor was subjective hunger different between the LED, MED and HED diets, respectively. Diet significantly affected body weight (F(2,10) = 4.62; P = 0.038), producing changes of -1.20, 0.02 and 0.95 kg, respectively, by day 14. CONCLUSION: Dietary ED can influence EI and body weight, since changes in amount eaten alone are insufficient to defend energy balance, when subjects feed on unfamiliar diets and diet selection is precluded. Comparison with our previous studies suggest that there was compensation in solid food intake when ED was altered using mixed diets (as in this study) compared to previous studies which primarily used fat or CHO to alter dietary ED.
Adult↗
Nutrition Society Medal Lecture. Appetite, feeding behaviour and energy balance in human subjects.
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Appetite Regulation↗
Methodological issues relating to the measurement of food, energy and nutrient intake in human laboratory-based studies.
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Clinical Laboratory Techniques↗
Carbohydrates and energy balance.
In the early 1970s carbohydrates (CHOs) were believed to induce overconsumption and excess fat deposition. They are now perceived to protect against these consequences. This paper evaluates the evidence for this change of interpretation by considering (1) the energy content of CHOs, (2) the energetic efficiency with which they are handled by the body, and (3) their effects on appetite, relative to other macronutrients. CHOs are the least energy-dense macronutrients (delta Hc) and exhibit the greatest variability in digestibility. Doubling the usual levels of nonstarch polysaccharides (fiber) may decrease digestibility of a Western diet by 5%. De novo lipogenesis from dietary CHO is energetically inefficient but very limited on Western diets, which are relatively high in fat. There appears to be a hierarchy (protein > CHO > fat) in the extent to which the stores of the macronutrients are autoregulated by oxidation. Excess CHO intake tends to promote storage (but not de novo synthesis) of fat. The thermogenic effects of CHO are therefore relatively limited on Western diets. Per MJ of energy ingested, macronutrients differentially affect satiety (protein > CHO > fat) under conditions where fat is disproportionately energy dense. Isoenergetically dense loads of fat and CHO exert less pronounced differences on satiety. Under some conditions HC diets promote excess energy intakes. There is little evidence that a CHO-rich diet, or one with intense sweeteners, promotes spontaneous weight loss.
Dietary Carbohydrates↗
High dose exercise does not increase hunger or energy intake in free living males.
OBJECTIVE: To examine the effects of a high dose (two high-intensity exercise sessions) of exercise on energy intake (EI) and subjective states (hunger and mood). DESIGN: Using a within subjects design, there were two treatment conditions, each of two consecutive days. SETTING: The Human Appetite Research Unit at Leeds University Psychology Department. SUBJECTS: Eight lean males who were regular exercisers were recruited from the student/staff population of Leeds University. INTERVENTIONS: The effects of the high dose of exercise Ex1 were compared with the effects on the day immediately after exercise (Ex2) and two consecutive days of no exercise (R1 and R2). EI was monitored using self-record food diaries and subjective states were tracked using a new Electronic Appetite Rating System (EARS). Heart rate and physical activity were also measured. RESULTS: Feelings of hunger were not elevated by the high dose of exercise on Ex1 or on the day after exercise (Ex2). In fact, average daily feeling of hunger on Ex1 was significantly lower compared with the average daily feeling of hunger on Ex2 (t = 3.15, d.f. = 7, P < 0.05), but not when compared with R1 or R2. EI and macronutrient intakes were not different on Ex1, Ex2, R1 or R2. Therefore, there were no increase in EI on Ex1 or Ex2 to account for the measured increase in exercise-induced energy expenditure (1200 kcal). Continuously monitored heart rate and activity profiles indicated that there was no difference in activity during the non-exercise periods between the four days. CONCLUSIONS: This study indicates that a high dose of exercise in one day failed to have any effect on EI within the same day or on the day immediately after exercise, compared with days of no exercise. These results demonstrate that an acute but substantial increase in energy expenditure (EE) due to intense exercise does not automatically increase hunger or EI within 48 h. This indicates the absence of any strong coupling between EE and EI in the short-term, probably as a result of food intake being held in place by environmental contingencies and short-term pre-absorptive physiological responses arising from eating itself.
Adult↗
Incremental dosage of the new antipsychotic mazapertine induces tolerance to cardiovascular and cognitive effects in healthy men.
OBJECTIVES: Mazapertine is a structurally novel antipsychotic compound with high affinity for D2, D3, 5-HT1a, and alpha 1 receptors. The objectives were to determine whether tolerance to orthostatic hypotension caused by this compound could be induced by slowly increasing the dose administered and to investigate its effect on cognitive and motor functions. METHODS: Thirteen healthy male subjects received incremental oral doses of mazapertine (from 5 to 50 mg over 7 days; n = 10) or placebo (n = 3) in part I and single doses in parts II (20 or 30 mg or placebo) and III (40 mg or placebo) in a double-blind fashion. Blood pressure, heart rate, cardiac hemodynamics, cognitive functions, and occurrence of acute extrapyramidal symptoms were investigated. RESULTS: Mazapertine appears to be safe and well tolerated when administered orally for 7 days to normal healthy men. No accumulation of serum prolactin occurred after multiple dosing, suggesting limited potential for inducing galactorrhea. The drug was rapidly absorbed, and kinetics appeared to be dose dependent, without accumulation. The elimination half-life was about 5 to 10 hours. No evidence of any positive or negative cognitive effects could be detected. Mild motor symptoms were observed only at high doses (not statistically significant). Mazapertine had a minimal effect on cardiac output and stroke volume. Tolerance to hypotension could be induced by slowly increasing the dose administered. CONCLUSIONS: Mazapertine is well tolerated when administered orally for seven days, and tolerance to hypotension can be induced by slowly increasing the dose administered. Therefore, nothing precludes further clinical testing on patients with schizophrenia.
Administration, Oral↗