bluuebunny/crossref_metadata_2025_split huggingface dataset:
HUMAN PERFORMANCE AFTER A BARBITURATE (HEPTABARBITONE)
Authors: BORLAND R.G. , NICHOLSON A.N. 
Published: July 2012

The residual effects of heptabarbitone given overnight were studied by an adaptive tracking technique. Decrements in performance were observed at the 10 h interval after 200 mg, at the 10 h and 13 h intervals after 300 mg and at the 10 h, 13 h, 16 h and 19 h intervals after 400 mg of the drug. Decrements in performance at each interval and the persistence of the effects were dose related.
Subjective assessments of performance correlated with measured performance, but the subjects, as a group, over‐estimated their performance after placebo and heptabarbitone. With heptabarbitone (400 mg) highly significant decrements in performance persisted to the 19 h interval after ingestion, but subjective assessments of performance to the 19 h interval did not differ significantly from subjective assessments of control activity of the day before.
Individual blood concentrations of heptabarbitone did not give a significant correlation with individual performance decrements, though the blood concentrations and performance decrements at each dose were related.
PRELIMINARY ASSESSMENT OF RX 72601, A NEW ANTICHOLINESTERASE IN MAN: REVERSAL OF COMPETITIVE NEUROMUSCULAR BLOCKADE
Authors: DETTMAR P.W. , METCALF G. , SMITH M.H. , GILLETT G.B. , HEDGES ANNMARIE , RICHENS A. 
Published: July 2012

The effect of RX 72601, neostigmine plus atropine, or saline on neuromuscular blockade with (+)‐tubocurarine was studied in a double blind trial in four healthy male volunteers.
The methods used to assess neuromuscular function were voluntary grip strength and indirectly evoked muscle twitches. The muscarinic action was assessed by measuring intestinal motility with a pressure sensitive radio pill, and auscultation of the abdomen. Blood pressure and pulse rate were also recorded. The degree of acetylcholinesterase inhibition achieved in whole blood was determined before and at intervals after the administration of the anticholinesterases.
Both RX 72601 (0.66‐0.83 mg) and neostigmine (2.5 mg) completely reversed the neuromuscular blockade produced by tubocurarine, but the time course of reversal differed. RX 72601 (0.66‐0.83 mg) produced similar inhibition of acetylcholinesterase in whole blood to neostigmine (2.5 mg). The doses of RX 72601 used caused minimal stimulation at muscarinic sites as evidenced by the limited effect on pulse rate and intestinal activity.
It was concluded that RX 72601 could be safely used to reverse the effects of neuromuscular blockade without the need for premedication with atropine.
AN ASSESSMENT OF GASTRIC EMPTYING BY BREATHALYSER
Authors: FINCH J.E. , KENDALL M.J. , MITCHARD M. 
Published: July 2012

A breathalyser has been used to measure blood alcohol levels at short intervals to produce an absorption curve which we have shown is reproducible.
Changes in the rate of absorption which reflect changes in gastric emptying times produced by metoclopromide and propantheline have been demonstrated.
The breathalyser technique described appears to offer a simple method of studying the effects of drugs on the rate of gastric emptying.
THE INFLUENCE OF DIPHENHYDRAMINE ON THE ABSORPTION OF METHAQUALONE IN MAN
Authors: WILLIAMS M.E. , DAVIS S.S. , POXON R. , KENDALL M.J. , MITCHARD M. 
Published: July 2012

The effects of diphenhydramine on the buccal absorption, in vivo absorption and the in vitro dissolution of methaqualone have been studied.
Diphenhydramine significantly reduced the buccal absorption of methaqualone and the effect was dose and pH dependent. In vivo, diphenhydramine did not alter the rate of absorption or the distribution of methaqualone in blood. In vitro, the presence of diphenhydramine increased the rate of dissolution of methaqualone and the effect was more marked when the particle size was small.
The reasons for and the implications of these apparently contradictory results are discussed and it is concluded that any increased efficacy resulting from combining diphenhydramine with methaqualone cannot be due to increased plasma drug levels.
THE CLINICAL SIGNIFICANCE OF INDOMETHACIN‐PROBENECID INTERACTION
Authors: BROOKS P.M. , BELL M.A. , STURROCK R.D. , FAMAEY J.P. , DICK W.C. 
Published: July 2012

The effect of the addition of probenecid to oral and rectal regimes of indomethacin was studied in three groups of rheumatoid arthritic patients.
The addition of probenecid increases plasma levels of indomethacin given both orally and rectally and significantly reduces the clinical parameters of joint inflammation.
The use of probenecid with indomethacin at night may be useful in reducing morning stiffness and pain. 4 Though indomethacin plasma levels are markedly raised during concurrent probenecid therapy remarkably few side effects were observed.
THE EFFECT OF DIFFERENT NEBULIZERS WITH AND WITHOUT INTERMITTENT POSITIVE PRESSURE BREATHING ON THE ABSORPTION AND METABOLISM OF SALBUTAMOL
Authors: SHENFIELD GILLIAN M. , EVANS MARION E. , PATERSON J.W. 
Published: July 2012

The absorption and metabolism of [3H]‐salbutamol have been studied to assess whether intermittent positive pressure breathing (IPPB) or a particular nebulizer have any advantages in delivering bronchodilator drugs to asthmatic patients.
[3H]‐salbutamol (10 mg) was given to asthmatic patients from either the Bird Mark 7 ventilator without intermittent positive pressure, the Bird micronebulizer attached to an electric air compressor, or the Wright's nebulizer attached to the same compressor.
All patients showed a high early plasma level of radioactivity due mainly to free salbutamol. This pattern suggests absorption from the lung and is similar to that seen after giving the drug from the Bird nebulizer using IPPB.
In all cases less than 20% of the original dose was absorbed by the patient.
Improvement in forced expiratory volume in one second (FEV1) was seen with all three treatments.
A PILOT STUDY OF ORALLY ADMINISTERED Δ1‐TRANS‐TETRAHYDROCANNABINOL IN THE MANAGEMENT OF PATIENTS UNDERGOING RADIOTHERAPY FOR CARCINOMA OF THE BRONCHUS
Authors: DAVIES B.H. , WEATHERSTONE R.M. , GRAHAM J.D.P. , GRIFFITHS R.D. 
Published: July 2012

Δ1 ‐trans‐tetrahydrocannabinol (Δ1‐THC; 10 mg) or a placebo was given orally on 7 days to two groups of six patients on a cross‐over pattern with 7 days rest between.
The patients were hospitalized, suffering from inoperable bronchogenic carcinoma, subjected to radiation therapy, and anxious.
Self‐rating mood scales were filled in before, and 2 and 6 h after ingestion on the first and seventh day of medication.
Records of sleep, pain, general well‐being, temperature, cardiovascular and gastrointestinal parameters were kept.
Δ1‐THC caused drowsiness and improved night sleep, reduced pain, increased fatigue and confusion and reduced elation and vigour; it caused slight tachycardia and hypotension as also did placebo.
The effects of Δ1‐THC were stronger after 2 h than 6 h and no tolerance had developed at 7 days.
The management of stressful patients was considered to have been improved by the drug.
PHYSIOLOGICAL AND PSYCHOLOGICAL EFFECTS OF ±‐PROPRANOLOL, +‐PROPRANOLOL AND DIAZEPAM IN INDUCED ANXIETY
Authors: TYRER P.J. , LADER M.H. 
Published: July 2012

Four equal‐sexed groups of eight normal subjects were given single doses of either (±)‐propranolol (120 mg), (+)‐propranolol (120 mg), diazepam (6 mg) or placebo using double‐blind procedure and their effects studied under three types of experimental stress and at rest.
Finger tremor, EEG, averaged auditory evoked response, skin conductance, heart rate and respiratory rate were measured at each time of testing, and subjects also completed performance tests (reaction time, tapping speed and symbol copying) and subjective mood scales.
Neither (+)‐ nor (±)‐propranolol had any beneficial effects on mood and physiological tests showed that, although adequate β‐adrenoceptor blockade was achieved, there was no evidence of sedation.
Diazepam reduced subjective anxiety, significantly lessened the main amplitude of the auditory evoked response and also reduced the proportion of slower rhythms in the EEG.
The results suggest that (+)‐ and (±)‐propranolol have no psychotropic effects on induced anxiety and that their modes of action are fundamentally different from that of diazepam.
PHYSIOLOGICAL RESPONSE TO PROPRANOLOL AND DIAZEPAM IN CHRONIC ANXIETY
Authors: TYRER P.J. , LADER M.H. 
Published: July 2012

Twelve chronically anxious psychiatric out‐patients, comprising six with somatic anxiety and six with psychic anxiety, were treated with (±)‐propranolol, diazepam and placebo for one week each in flexible dosage using a balanced cross‐over experimental design.
After each treatment, in addition to ratings completed by patient and psychiatrist, finger tremor, EEG, averaged auditory evoked response, skin conductance, heart and respiratory rate were measured.
Diazepam significantly increased the amount of fast activity (13.5–26 Hz) in the EEG but produced few peripheral effects apart from a reduction in finger tremor.
Propranolol had no central physiological effects but reduced both pulse rate and finger tremor.
The physiological effects of propranolol in chronic anxiety are different from those of diazepam and therapeutic benefit appears to be due to a direct effect on certain somatic symptoms.
THE CLINICAL PHARMACOLOGY OF SALMEFAMOL
Authors: EVANS MARION E. , SHENFIELD GILLIAN M. , PATERSON J.W. 
Published: July 2012

The absorption, excretion and metabolism of [3H]‐salmefamol, a new sympathomimetic bronchodilator drug, have been studied in asthmatic patients.
Following oral administration of 1 or 2 mg to four patients the drug was well absorbed, peak plasma levels occurring from 0.6‐2.0 h after administration. An improvement in forced expiratory volume in 1 s (FEV1) (ranging from 12–50% above baseline) was seen.
Following aerosol administration of 0.22‐0.34 mg to four patients a rapid rise in FEV1 was seen (range 26–117%). The plasma and urinary pictures following this route were similar to those seen after oral administration, suggesting that the majority of the dose was swallowed.
Very little free salmefamol was found in plasma or urine, the majority being present as metabolites. Urinary radioactivity was mainly present in the form of sulphate conjugates of at least two compounds, one of which was salmefamol. The other compound has not been identified but it is suggested that it may be an active metabolite.
THE INFLUENCE OF ELEVATED PLASMA HYDROCORTISONE CONCENTRATIONS ON ANTIPYRINE METABOLISM IN MAN
Authors: FLANAGAN R.J. , RICHENS A. 
Published: July 2012

The plasma half‐life of antipyrine was estimated overnight in four healthy volunteers on two separate occasions, one during i.v. infusion of hydrocortisone (3 mg/h) and the second during an infusion of normal saline.
The plasma fluorogenic corticosteroid concentration averaged 12.5 μg/100 ml during saline infusion, increasing to 20.1 μg/100 ml during hydrocortisone infusion.
The mean antipyrine half‐life increased from 9.7 h during saline infusion to 12.6 h during hydrocortisone infusion.
No consistent change was found in the apparent volume of distribution or urinary excretion of antipyrine, or of the urinary excretion of D‐glucaric acid.
The stimulation by hydrocortisone of antipyrine metabolism demonstrated by other workers has not been found.
THE ABSORPTION AND METABOLISM OF A STANDARD ORAL DOSE OF LEVODOPA IN PATIENTS WITH PARKINSONISM
Authors: BERGMANN S. , CURZON G. , FRIEDEL J. , GODWIN‐AUSTEN R.B. , MARSDEN C.D. , PARKES J.D. 
Published: July 2012

The metabolism of a standard oral dose of levodopa was studied in forty‐two patients with Parkinsonism. Plasma levodopa and 3‐o‐methyldopa concentrations were estimated at intervals for 8 h after ingestion and the concentration of homovanillic acid (HVA) in the lumbar cerebrospinal fluid (CSF) was measured at 8 hours. Clinical responses 3 months after the test were compared with these findings.
Although therapeutic benefit correlated significantly with calculated estimates of both plasma levodopa concentration and CSF HVA at optimal levodopa dose, individual values were widely scattered. There was no significant correlation between toxic effects and plasma levodopa or CSF HVA; and 3‐o‐methyldopa concentrations similarly did not show a significant correlation with either toxic or therapeutic effects.
Blood and CSF levels of levodopa or the metabolites measured in this study were not significantly altered by concurrent treatment with either anticholinergic drugs or amantadine nor by previous treatment with levodopa.
ACETYLATION OF PROCAINE AMIDE IN MAN STUDIED WITH A NEW GAS CHROMATOGRAPHIC METHOD
Authors: KARLSSON E. , MOLIN LILIAN , NORLANDER B. , SJÖQVIST F. 
Published: July 2012

A specific gas‐chromatographic method was developed for determination of N‐acetylprocaine amide in plasma and urine, using 4‐amino‐N‐(2‐piperidinoethyl)benzamide as an internal standard. The investigation was performed in 50 cardiac patients who had reached steady‐state plasma concentrations of procaine amide.
The plasma concentrations of the acetylated metabolite varied between 1.0 and 15.0 μg/ml and were thus of the same order of magnitude as those of the parent drug. Especially high plasma levels of the metabolite were seen in patients with poor kidney function.
The urinary excretion of the metabolite varied markedly between individuals and ranged between 6 and 52% of the administered daily dose. There was a clear tendency towards higher rates of acetylation of procaine amide in patients with short plasma half‐lives of isoniazid, i.e. the phenotype rapid acetylators. Because of coexisting therapy with other drugs and impaired renal function in some patients studies are required in healthy human volunteers to ascertain whether the acetylation of procaine amide and isoniazid are mediated by the same enzyme system.
THE EFFECTS OF ORAL AH 5158, A COMBINED α AND β‐ADRENOCEPTOR ANTAGONIST, IN HEALTHY VOLUNTEERS
Authors: RICHARDS D.A. , WOODINGS E.P. , STEPHENS M.D.B. , MACONOCHIE J.G. 
Published: July 2012

In healthy male volunteers after single oral doses, AH 5158 produced inhibition of exercise induced tachycardia, falls in systolic and diastolic pressure at rest and in response to exercise, which are probably related to combined β‐ and α‐adrenoceptor antagonism.
At increasing doses from 100 mg to 400 mg there exists a dose related antagonistic effect, though the dominant effect of β‐adrenoceptor antagonism is more easily demonstrable than is α antagonism.
As indicated by the pattern of pharmacological effects, absorption of the oral drug is good and the duration of action of a 400 mg dose is approximately 8 hours.
Despite being administered in β‐adrenoceptor blocking doses, AH 5158 had no adverse effects upon peak expiratory flow at rest or in response to exercise.
It is concluded that the pharmacological profile of this combined α‐ and β‐adrenoceptor antagonism suggests a potential therapeutic role as an antihypertensive drug.
PLASMA DOPA CONCENTRATIONS AFTER DIFFERENT PREPARATIONS OF LEVODOPA IN NORMAL SUBJECTS
Authors: MORRIS J.G.L. , PARSONS R.L. , TROUNCE J.R. , GROVES M.J. 
Published: July 2012

The concurrent administration of levodopa with a decarboxylase inhibitor produced a plasma concentration/time curve comparable with 1/4 to 1/5 of the dose of levodopa given alone.
There was no evidence to suggest that the decarboxylase inhibitor slowed the rate of elimination of levodopa from plasma.
Metoclopramide (Maxolon) increased the rate of levodopa absorption. Higher plasma concentrations of levodopa during the first 2 h after dosing were followed by lower plasma concentrations during the third and fourth hours. The amount of levodopa absorbed after Larodopa as indicated by the AUC was not altered by adding metoclopramide.
None of the current preparations of levodopa produced sustained plasma concentrations.
In vitro testing confirmed that Brocadopa Temtabs tablets disintegrate and dissolve slowly. In vivo, Brocadopa Temtabs behaved as a slow release preparation but it did not produce sustained plasma concentrations of levodopa.
BIOTRANSFORMATION AND EXCRETION OF LORAZEPAM IN PATIENTS WITH CHRONIC RENAL FAILURE
Authors: VERBEECK R. , TJANDRAMAGA T.B. , VERBERCKMOES R. , DE SCHEPPER P.J. 
Published: July 2012

To evaluate the effect of end‐stage renal insufficiency and haemodialysis on the elimination of lorazepam, single oral doses of the drug (2.5 mg) were administered to normal subjects and patients with chronic renal failure (Ccr: less than 2 ml/min) in the interdialysis period and during haemodialysis.
The concentration of lorazepam and its major metabolite, lorazepam‐glucuronide, were assayed using electron capture g.1.c.
Plasma half‐life (T1/2) of unchanged lorazepam in the patient group (11.3 ± 0.6 h) was not different from that obtained in normals (11.1 ± 0.9 h).
Only minor quantities of the unchanged drug could be recovered in the 24 h urine in both groups: 0.3% of the ingested dose in normals and trace amounts in the patient group.
No unchanged lorazepam could be detected in the ultrafiltrate from the coil kidney. Since the lower sensitivity of the method is about 5 ng/ml, this would indicate the in vivo binding of the active drug to plasma proteins to be at least 70%.
The effect of haemodialysis on lorazepam plasma T1/2 was also insignificant (9.4 ±1.0 h).
Urinary excretion of lorazepam‐glucuronide was found to be considerably decreased in chronic renal failure associated with accumulation of high concentrations of this conjugate in plasma during days after a single oral dose. The plasma T1/2 of this conjugate in normals was 20.7 ± 2.1 h.
Roughly 35% of this main metabolite's concentration in plasma was detected in the ultrafiltrate from the coil kidney indicating the dialyzability of this conjugate and that the extent of plasma protein binding of lorazepam‐glucuronide in vivo was approximately 65%.
The above results indicate that after a single oral dose (2.5 mg) the biotransformation of lorazepam to its glucuronide conjugate remains unaltered and that high concentrations of this metabolite accumulate in plasma in the presence of severe renal function impairment.
EFFECT OF DIAZEPAM AND FOSAZEPAM (A SOLUBLE DERIVATIVE OF DIAZEPAM) ON SLEEP IN MAN
Authors: NICHOLSON A.N. , STONE BARBARA M. , CLARKE CORAL H. 
Published: July 2012

The effect of diazepam (5 mg and 10 mg), and fosazepam (60 mg and 80 mg), a soluble derivative of diazepam, on sleep was studied in six healthy adult males using electroencephalography for sleep measures, and analogue scales for subjective assessments of well‐being and sleep quality. The effect of diazepam was limited to the night of ingestion, but the effect of fosazepam was carried over to the next night and so modified sleep for about 30 h after ingestion.
Effects on total sleep time were limited to the night of ingestion. There were increases with diazepam (10 mg) (P=0.05), and with fosazepam (60 mg and 80 mg) (P = 0.001). For the night of ingestion sleep onset latencies were shortened, and awakenings were reduced by both drugs. The latency to stage 3 was shortened by fosazepam (60 mg and 80 mg) (P = 0.05).
The low and high dose of each drug reduced the duration (min) of stage 0 sleep (P = 0.01), but fosazepam also reduced the duration (min) of stage 1 sleep (P = 0.001), and there was an increase in stage 2 sleep (P = 0.01). With fosazepam there were carry over effects to the next night with reduction of stage 1 sleep (P = 0.05). There were no effects on the duration of stage 3, but there was evidence that stage 4 activity was reduced during the recovery night after ingestion of fosazepam (80 mg). No effects were observed on REM sleep.
Subjects reported an improved sense of well‐being during the day after ingestion of diazepam and fosazepam, and with fosazepam they reported improved sleep. Correlations were calculated for sleep measures and subjective assessments.
EFFECT OF A METABOLITE OF DIAZEPAM, 3‐HYDROXYDIAZEPAM (TEMAZEPAM), ON SLEEP IN MAN
Authors: NICHOLSON A.N. , STONE BARBARA M. 
Published: July 2012

The effect of 3‐hydroxydiazepam (temazepam, 10 mg and 20 mg) on sleep was studied in six healthy adult males using electroencephalography for sleep measures, and analogue scales for subjective assessments of well‐being and sleep quality. The effects were compared with diazepam (5 mg and 10 mg).
Effect on total sleep time was restricted to the night of ingestion. There was no change in total sleep time after temazepam (10 mg), but with 20 mg total sleep time was increased (P = 0.01). Sleep onset latencies and awakenings were markedly reduced.
Temazepam reduced the duration (min) of stage 0 (P = 0.05) and stage 1 (P = 0.01) sleep, and the effect on stage 1 was seen during each two hourly interval of sleep (P= 0.05). No effects were observed with stage 3, 3+4 and REM sleep, except that the appearance of the first REM period was delayed with temazepam (20 mg) (P = 0.001).
The subjects, as a group, reported improved sleep, but subjective assessments of well‐being were not altered. Correlations were calculated for sleep measures and subjective assessments.
A COMPARISON OF SOME PHYSIOLOGICAL AND PSYCHOLOGICAL EFFECTS OF PROPRANOLOL AND DIAZEPAM IN NORMAL SUBJECTS
Authors: ASHTON HEATHER , MILLMAN J.E. , TELFORD ROSEMARY , THOMPSON J.W. 
Published: July 2012

Some central and peripheral effects of orally administered propranolol (60 mg), diazepam (5 mg) and placebo were compared in normal subjects.
The central effects measured were changes in magnitude of the contingent negative variation (CNV) and subjective anxiety ratings; the peripheral effects were changes in heart rate, blood pressure, galvanic skin response and hand steadiness.
After diazepam there was a decrease in CNV magnitude and in the level of subjective anxiety; there was a slight fall in blood pressure but little change in heart rate.
After propranolol, on the other hand, there was no significant change in CNV magnitude or anxiety rating, but a significant fall in heart rate and systolic blood pressure.
It is concluded that, at the dosage used, propranolol, unlike diazepam, does not affect the central mechanisms determining CNV magnitude or subjective anxiety. The relationship of this finding to the use of β‐adrenergic receptor blockers in clinical anxiety states is discussed.
CSF CONCENTRATIONS AND SERUM PROTEIN BINDING OF CARBAMAZEPINE AND CARBAMAZEPINE‐10, 11‐EPOXIDE IN EPILEPTIC PATIENTS
Authors: JOHANNESSEN S.I. , GERNA M. , BAKKE J. , STRANDJORD R.E. , MORSELLI P.L. 
Published: July 2012

Serum and CSF samples of patients receiving chronic carbamazepine treatment were analysed.
Daily fluctuations in serum levels of carbamazepine and carbamazepine‐10, 11‐epoxide did not appear to be related to the dosage schedule, but some patients tended to have lower fluctuations when the carbamazepine was given more frequently.
The epoxide/carbamazepine serum ratios varied greatly from patient to patient, and also fluctuated during the day for the same patient.
Carbamazepine and carbamazepine‐10, 11‐epoxide were present in CSF in concentrations ranging from 19 to 34% and 26 to 71% of the serum concentrations, respectively.
There was a significant relationship between the free fraction of both drugs evaluated in vivo and the CSF/serum ratios.
The need for a careful evaluation of the possible clinical effect of the epoxide is stressed.