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  • 1
    Electronic Resource
    Electronic Resource
    EFFECTS OF ENVIRONMENTAL CHEMICALS ON THE METABOLISM OF DRUGS, CARCINOGENS, AND NORMAL BODY CONSTITUENTS IN MAN (1971)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 179 (1971), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1971.tb46897.x
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  • 2
    Electronic Resource
    Electronic Resource
    Hydrolysis of suxamethonium by plasma from subjects responding to the drug with prolonged apnoea, and by plasma from their relatives (1969)
    Springer
    European journal of clinical pharmacology 2 (1969), S. 6-12 
    Details
    ISSN: 1432-1041
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The hydrolysis of benzoylcholine, 0.05 mM, butyrylcholine, 10 mM, and suxamethonium, 0.025 mM, by the plasma of 10 subjects who developed prolonged apnoea following suxamethonium administered during anaesthesia, were measured. Plasmas from all available relatives in four families were similarly studied. The plasma of 3 subjects contained only atypical cholinesterase and hydrolysed suxamethonium, relative to butyrylcholine, at a rate of only 1.6% of that seen with usual human cholinesterase. One subject appeared to have only atypical cholinesterase on the basis of dibucaine and fluoride numbers. Suxamethonium hydrolysis, however, was sixteen times greater than that for the 3 homozygous atypical subjects. Family studies and inhibition of butrylcholine hydrolysis by decamethonium established that this subject was heterozygous with about 20% of the total cholinesterase in the usual form. Two other subjects were also heterozygous for usual and either atypical or fluoride resistant genes. One of them hydrolysed suxamethonium at 25% of the usual rate, but the other had a normal rate of suxamethonium hydrolysis. Four subjects had no detectable anomaly of plasma cholinesterase, and hydrolysed suxamethonium normally. The apparent affinity of suxamethonium for usual and atypical cholinesterase was also determined and the significance of measurements of the hydrolysis of suxamethonium in relation to prolonged apnoea produced by the drug is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00404178
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  • 3
    Electronic Resource
    Electronic Resource
    The effect of bupropion, a new antidepressant drug, and alcohol and their interaction in man (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 75-80 
    Details
    ISSN: 1432-1041
    Keywords: bupropion ; alcohol interaction ; healthy volunteers ; performance ; autonomic functions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of bupropion and ethanol were examined alone and in combination in a placebo controlled, double-blind, crossover study in 12 healthy volunteers. Results were subjected to analysis of variance and differences ofp〈0.05 taken as significant. In the main study using the Wilkinson auditory vigilance test, no active treatment or combination of treatments produced significant change compared with placebo. However, when compared with bupropion 100 mg, vigilance was significantly impaired by 32 ml alcohol alone though not when combined with bupropion. No significant changes in reaction time or short term memory occurred. Visual analogue scales indicated that the subjects were mentally slower after alcohol 32 ml than after placebo. Combination of bupropion 100 mg with alcohol 32 ml abolished this difference. A similar pattern occurred with group ratings indicating mental sedation. Subjects were clearly able to differentiate between the 16 ml and 32 ml doses of alcohol when assessing their degree of inebriation. Combination of bupropion with alcohol made no difference to the ratings of inebriation. The top dose of alcohol tended to increase energy in the low frequency EEG bands. Combination of the top alcohol dose with bupropion, however, produced a significant reversal with lowered energy in the 4–7.5 Hz band. Combination of bupropion with alcohol failed to change the blood alcohol concentration achieved.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02395210
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  • 4
    Electronic Resource
    Electronic Resource
    A comparison of methods for assessing the sedative effects of diphenhydramine on skills related to car driving (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 477-482 
    Details
    ISSN: 1432-1041
    Keywords: diphenhydramine ; antihistamine drugs ; sedation ; car driving skills ; body sway ; adaptive tracking ; reaction time
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A double blind cross-over study was performed to compare the sensitivity of “oof road” driving with that of laboratory tests of driving-related skills to drug induced sedation. Twelve experienced drivers (6 M, 6 F) received single oral doses of the H1-antagonist diphenhydramine 25, 50 and 100 mg and placebo. Each treatment was administered on 2 separate occasions, once in the driving school when real driving skills were assessed and again in the laboratory when performance of an adaptive tracking task, body sway and visual reaction were measured. On all occasions subjects assessed their own performance and alertness/sedation using visual analogue scales. Data were subjected to analysis of variance and differences assessed by Newman Keul's test. Diphenhydramine failed to impair driving performance at any dose while all doses produced significant changes in each of the 3 laboratory tests. Subjects rated themselves sedated after all 3 doses of active drug in the laboratory but only after the 100 mg dose in the driving school. Tests performed in the psychopharmacology laboratory appear to be more sensitive to the sedative effects of diphenhydramine than tests of “off road” driving. The implications are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00549598
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  • 5
    Electronic Resource
    Electronic Resource
    The disposition of bupropion and its metabolites in healthy male volunteers after single and multiple doses (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 97-103 
    Details
    ISSN: 1432-1041
    Keywords: bupropion ; metabolites ; pharmacokinetics ; single and multiple dose ; side-effects ; enzyme induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of bupropion and 3 of its basic metabolites were determined in 8 young, healthy, male volunteers after single and multiple oral doses of bupropion. Plasma profiles were obtained: 1) after a single 100 mg oral dose of bupropion hydrochloride, 2) following administration of 100 mg 8-hourly for 14 days and 3) again after a single 100 mg dose 14 days later. Plasma concentrations of the parent drug and metabolites were determined by high-performance liquid chromatography. Saliva secretion and pupil diameters were measured, subjective assessments of sleep made using visual analogue scales and side effects, blood counts and biochemistry were monitored. After the first dose mean elimination half lives (t1/2) of bupropion, and metabolites I and II were 8, 19 and 19 h respectively. On repeated administration there was little accumulation of the parent drug and no evidence for induction of its own metabolism. Accumulation of I was consistent with its rate of elimination after single doses while that of II was greater than predicted with prolongation of t1/2 to 35 h. Metabolite III was barely detectable after single doses but its accumulation on multiple dosing was consistent with its long half life (35 h) determined on occasion 2. Saliva secretion was significantly reduced during the multiple dosing period but there were no complaints of dry mouth. Subjective assessments of sleep were not significantly altered though one subject reported vivid dreams. There were no other adverse reactions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547376
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  • 6
    Electronic Resource
    Electronic Resource
    A technique for studying the effects of drugs on human sweat gland activity (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 221-226 
    Details
    ISSN: 1432-1041
    Keywords: Human sweat gland activity ; acetylcholine ; atropine anticholinergic assessment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A technique is described for studying the effects of drugs with anticholinergic properties on human forearm sweat glands. The response of sweat glands to intradermal injections of increasing concentrations of acetylcholine (ACh) in saline was measured. The number of glands activated was recorded by painting the injection area with a plastic impression paint one minute after injection. The plastic impression was removed using “Sellotape”, mounted on a 35 mm slide, projected, and glands counted. Standardisation of conditions was important with respect to ambient temperature and physical activity of subject in order to reduce spontaneous sweat gland activity. The dose response relationship was similar for men and women. In a double blind, controlled, cross over investigation, 8 subjects (4M and 4 F) received lactose dummy and atropine sulphate 1 mg p. o. Sweat gland activity, salivation, heart rate, pupil size and visual near point were measured before and 1 and 2 h after treatment. Significant (P〈0.05) reduction occurred in the number of glands responding to 140 and 550 µM ACh and also in the salivary secretion rate 2 h after atropine, compared with values after lactose dummy. No significant changes in pupil size, visual near point or heart rate occurred. It is suggested that inhibition of the response of forearm sweat glands to ACh is at least as sensitive as other measures of parasympathetic functions for assessing parasympatholytic agents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02089963
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  • 7
    Electronic Resource
    Electronic Resource
    The effect of bupropion, a new antidepressant drug, and alcohol and their interaction in man (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 75-80 
    Details
    ISSN: 1432-1041
    Keywords: bupropion ; alcohol interaction ; healthy volunteers ; performance ; autonomic functions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of bupropion and ethanol were examined alone and in combination in a placebo controlled, double-blind, crossover study in 12 healthy volunteers. Results were subjected to analysis of variance and differences ofp〈0.05 taken as significant. In the main study using the Wilkinson auditory vigilance test, no active treatment or combination of treatments produced significant change compared with placebo. However, when compared with bupropion 100 mg, vigilance was significantly impaired by 32 ml alcohol alone though not when combined with bupropion. No significant changes in reaction time or short term memory occurred. Visual analogue scales indicated that the subjects were mentally slower after alcohol 32 ml than after placebo. Combination of bupropion 100 mg with alcohol 32 ml abolished this difference. A similar pattern occurred with group ratings indicating mental sedation. Subjects were clearly able to differentiate between the 16 ml and 32 ml doses of alcohol when assessing their degree of inebriation. Combination of bupropion with alcohol made no difference to the ratings of inebriation. The top dose of alcohol tended to increase energy in the low frequency EEG bands. Combination of the top alcohol dose with bupropion, however, produced a significant reversal with lowered energy in the 4–7.5 Hz band. Combination of bupropion with alcohol failed to change the blood alcohol concentration achieved.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00553158
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  • 8
    Electronic Resource
    Electronic Resource
    Changes in the human light reflex as a measure of the anticholinergic effects of drugs. A comparison with other measures (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 21-25 
    Details
    ISSN: 1432-1041
    Keywords: pupillometry ; light reflex ; atropine ; nortryptyline ; procyclidine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single oral doses of atropine, nortriptyline, procyclidine and lactose dummy were administered double-blind to eight healthy young subjects in a balanced, crossover study. Television pupillometry was used to measure the anticholinergic effects of these drugs on the pupil diameter in darkness and the reflex response to light flashes. The sensitivity of this method was compared with conventional autonomic function tests, viz. salivary secretion, radial pulse, forearm sweat gland activity and distance to visual near point. Visual analogue scales were used to obtain subjective measures of sedative drug effects. The expected inhibition of parasympathetic activity was found in most instances with two exceptions: firstly, that nortriptyline failed to affect the pupil despite causing a tachycardia and secondly, that procyclidine gave a bradycardia. The results are discussed with reference to the possible advantages of television pupillometry over conventional pupil measurement in the detection of anticholinergic drug effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563554
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  • 9
    Electronic Resource
    Electronic Resource
    Alcohol and bupropion pharmacokinetics in healthy male volunteers (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 627-630 
    Details
    ISSN: 1432-1041
    Keywords: bupropion ; ethanol ; pharmacokinetic interaction ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A study was performed to determine whether there is a pharmacokinetic interaction between alcohol and the novel antidepressant bupropion. In the first part 8 healthy male volunteers received single doses of 100 mg bupropion hydrochloride orally on 2 occasions accompanied by either ethanol in orange or plain orange drink according to a balanced cross over design. Plasma bupropion concentrations were determined by radioimmunoassay and kinetics analysed with the aid of NONLIN. Blood alcohol levels were assessed by breathalyser. The disposition of bupropion was adequately described by a 2 compartment model and kinetic parameters were not significantly altered by the presence of alcohol. In the second part of the study the same subjects received 40 ml ethanol in orange drink 3.5 h after ingestion of 100 mg bupropion or dummy tablet in a double blind cross over fashion. Bupropion did not affect alcohol kinetics. In contrast to many other psychotropic drugs there is no evidence for a kinetic interaction between bupropion and alcohol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543497
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  • 10
    Electronic Resource
    Electronic Resource
    Pharmacodynamic and pharmacokinetics of BW 825C: A new antihistamine (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 197-204 
    Details
    ISSN: 1432-1041
    Keywords: triprolidine ; BW 825C ; pharmacokinetics ; pharmacodynamics ; sedation ; intradermal histamine ; human performance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The new H1-receptor antagonist BW 825C and triprolidine (2.5 and 5 mg) were administered to 12 healthy male volunteers in a double blind placebo controlled, balanced, crossover design. Histamine antagonism was measured by assessment of flare and weal areas after intradermal injection of histamine. The 2 compounds were approximately equipotent in blocking the flare and weal response to intradermal histamine and had a similar duration of action. Triprolidine impaired performance of vigilance and reaction time (p〈0.05) compared with placebo while BW 825C did not. Drowsiness measured using visual analogue scales followed both triprolidine treatments, but not BW 825C. BW825C had a plasma half-life (t1/2) of 1.7±0.2 h and triprolidine of 4.6±4.3 h. The peak plasma level of BW 825C was approximately 6 times that of triprolidine. It was concluded that BW 825C might be a clinically active H1-antagonist with reduced sedative side-effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609692
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