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  • 1
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: L(+)pseudoephedrine ; different formulations ; plasma concentrations ; cardiovascular and subjective effects in man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of L(+)pseudoephedrine administered in clinically used dosages were determined by gas liquid chromatography using a nitrogen sensitive detector. They were measured after administration of an immediate release formulation (Sudafed) given in either a single dose of 180 mg, or three divided doses of 60 mg, and also after administration of two different sustained release preparations containing 180 mg. Ten subjects each received five treatment regimes, administration being ordered in a balanced design based on 2 five sided Latin squares. Significant differences were found between plasma concentrations and rates of urinary excretion of L(+)pseudoephedrine following administration of the different preparations. Peak plasma concentrations were greatest after 180 mg of the immediate release preparation while more sustained elevations of concentration followed administration of both sustained release preparations and the immediate release preparation in repeated doses. Despite these differences in plasma concentration significant differences in heart rate, blood pressure, or subjective ratings of mental state rarely occured, and the reasons for this are discussed. In a second study, one of the sustained release preparations was administered to 10 subjects at a dose of 180 mg twice daily for two weeks, and plasma concentrations and effects were measured. L(+)pseudoephedrine plasma levels reached a plateau in 3 days producing increased heart rate initially insomnia occurred but this disappeared after 3 days.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 6 (1973), S. 163-169 
    ISSN: 1432-1041
    Keywords: Dexamphetamine ; 1-benzylpiperazine ; human psychomotor and vigilance tests
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of dexamphetamine (1 mg to 7.5 mg) and 1-benzylpiperazine (20 mg to 100 mg) on performance tests and cardiovascular responses were measured in two groups of 12 normal subjects. Drugs and dummy control were administered orally under double blind conditions at weekly intervals according to a balanced design. Significant (p〈0.05) improvement occurred in an auditory vigilance test following both drugs, and this test was sufficiently sensitive to detect the changes produced by dexamphetamine 1 mg at the time of peak drug action. Subjective effects were only detected by the subjects after dexamphetamine 7.5 mg and 1-benzylpiperazine 100 mg. Significant changes attributable to drug treatment were not found in tests of short duration such as tapping rate, hand steadiness and arithmetic. Both drugs produced significant increases in heart rate and systolic blood pressure. It was concluded that 1-benzylpiperazine has psychomotor stimulant activity similar to dexamphetamine and that this was most reliably detected by using a prolonged signal detection test. The effects of 1-benzylpiperazine eye-drops (2%) on pupil diameter was investigated in 6 subjects who had had one eye pretreated with guanethidine (5%) eye-drops. 1-Benzylpiperazine gave effects similar to tyramine but significantly different from methoxamine indicating an indirect sympathomimetic action.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1041
    Keywords: histamine antagonists ; triprolidine ; clemastine ; skin responses ; circadian rhythm ; psychomotor tests ; subjective effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of triprolidine hydrochloride 1.25, 2.5 and 5 mg, clemastine 1 and 2 mg and lactose dummy administered orally, in a balanced order, at weekly intervals to 12 healthy volunteers, on the flare and weal responses to intradermal histamine injection, and also on both subjective effects and objective psychomotor tests were examined. The histamine response was significantly larger at 09.00 h falling through the day but increasing by late afternoon. Triprolidine produced a dose-related antagonism of both flare and weal response maximal at 3 h and wearing off after the lower doses at 8 h. Clemastine by contrast produced poor antagonism of histamine at 3 h but a marked effect at 5.5 and 8 h. Auditory vigilance was significantly (p〈0.05) impaired by all doses of triprolidine 1 to 2 h after administration, but no change followed clemastine at this time. When tested 6 to 7 h after administration significant impairment followed both doses of clemastine but only the 5 mg dose of triprolidine. Both drugs prolonged reaction time in a dose-related manner at 2.5 and 5.0 h but the effects had worn off at 7 h. Digit symbol substitution was impaired by the top doses of both antihistamines but short term memory was unaffected. Subjective effects measured using analogue lines reflected the effects in the vigilance test, in that drowsiness and mental impairment were noted early after triprolidine, while clemastine produced maximal effects at 5 h. Subjects were ranked in order of magnitude of inhibition of both flare and weal, and impairment of vigilance, prolongation of reaction time and subjective drowsiness score. There was no indication of a significant correlation, using Spearman's test, between antagonism of histamine and effects on the central nervous system.
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  • 5
    ISSN: 1432-1041
    Keywords: BW443C ; enkephalin ; opioid peptide ; healthy volunteers ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied 16 healthy men to evaluate preliminary pharmacodynamics and kinetics of BW443C given by i.v. infusions. Four volunteers received escalating doses at weekly intervals, starting at 0.1 µg·kg−1 for 60 min and increasing to a maximum of 2.0 µg·kg−1·min−1 for 180 min. Subsequently 12 different subjects received single i.v. infusions of 10 µg·kg−1·min−1 for 20 min. Subjective effects were reported and objective measurements made of central nervous and cardiovascular effects. Blood was sampled at intervals on all occasions, plasma concentrations were determined by radioimmunoassay and pharmacokinetic profiles were analysed using NONLIN. Dry mouth and some nasal stuffiness were reported and postural hypotension occurred in 5/16 subjects at plasma concentrations 〉0.8 µg·ml−1. Supine blood pressure was well maintained in all subjects and hypotension resolved within 60–90 min of discontinuing the infusion. There was no evidence of sedation, mood change, nausea, vomiting, miosis, change in accomodation or respiratory depression. Rapid infusions produced transient feelings of warmth, heavy eyelids, heavy legs, and increased bowel sounds, which resolved despite increasing plasma concentrations. The disposition of the peptide was adequately described by a 2-compartment model with a mean ± SD plasma clearance of 123±18 ml·min−1 and a half-life of 2.0±0.4 h.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1041
    Keywords: enkephalin analogue (443C81) ; analgesia ; cold pain ; healthly volunteers ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 443C81 is a synthetic enkephalin thought to act on peripheral opiate receptors. The analgesic, central, cardiovascular and endocrine effects of two i.v. doses of 443C81 were investigated in 12 healthy male volunteers. Its effects were compared with those of placebo and the classical opiate dipipanone given orally using a double dummy design. 443C81 produced dose-related analgesia; dipipanone 10 mg had a greater effect than the high dose 443C81. In contrast to dipipanone, 443C81 did not cause significant miosis or reduce minute volume on rebreathing CO2 and there was no evidence of sedation. Dry mouth was reported frequently and associated with reduced salivation after all active treatments. Both 443C81 and dipipanone increased circulating prolactin and growth hormone and reduced cortisol levels. This novel enkephalin appears to possess analgesic activity and some other properties of opiates but is devoid of clinically relevant narcotic effects.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 14 (1978), S. 221-226 
    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.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 26 (1984), S. 627-630 
    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
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 12 (1977), S. 181-186 
    ISSN: 1432-1041
    Keywords: Histamine antagonists ; triprolidine ; central nervous effects ; normal volunteers ; tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A double blind controlled study was conducted on 8 healthy adult volunteers to assess the effects of repeated doses of the histamine antagonist, triprolidine, on performance tests and subjective feelings. A comparison was made between the effects of triprolidine 5 mg and lactose dummy using four different treatment schedules under double blind conditions. Subjects were treated on two consecutive days each week for four weeks. A schedule of tests was given on each of the treatment days and results were analysed by the method of analysis of variance, values of p〈0.05 being taken as significant. Following triprolidine, impairment occurred in all performance tests, specifically, auditory vigilance, short term memory, reaction time, digit symbol substitution and tapping. Similarly there was significant mental and physical sedation. Evidence of a reduced effect of triprolidine on day 2 when triprolidine drug had been given on day 1 occurred in the tapping test and the change in mental sedation from pre to post treatment. However in all tests and subjective ratings the effect of triprolidine on day 2 was lessened by pretreatment with triprolidine on day 1, though this only achieved significance in the two variables mentioned. No evidence for increased effect of drug due to cumulation was obtained. It was concluded that tolerance to the effect of triprolidine on the nervous system begins to occur within 24 h with repeated dosing.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 6 (1973), S. 170-176 
    ISSN: 1432-1041
    Keywords: 1-Benzylpiperazine ; dexamphetamine ; prediction of drug abuse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The subjective, behavioural and autonomic effects of dexamphetamine 10 mg, 1-benzylpiperazine 100 mg and lactose dummy were compared in a group of 18 former amphetamine addicts. All subjects received the three preparations according to a balanced design under double blind conditions. 1-Benzylpiperazine and dexamphctamine produced indistinguishable subjective effects and both were liked. The effects of both compounds differed significantly from the effects following the dummy preparation. Increases in pulse rate and both systolic and diastolic blood pressure were similar following the two active compounds, but 1-benzylpiperazine produced pupillary dilation whereas no significant change in pupil size followed dummy or dexamphetamine. It was concluded that 1-benzylpiperazine is a compound liable to abuse by an addict population, and that this type of study might be of value in predicting abuse liability of other new drugs.
    Type of Medium: Electronic Resource
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