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Biomedical subjects

A Rushton

Publications and source records attributed to A Rushton.

10 recordsLinked to original sources
PubMed1992

The effects of a selective 5-HT2 receptor antagonist (ICI 170,809) on platelet aggregation and pupillary responses in healthy volunteers.

1. ICI 170,809 (2-(2-dimethylamino-2-methylpropylthio)-3-phenylquinoline hydrochloride) is a potent 5-hydroxytryptamine (5-HT) type 2 postsynaptic receptor antagonist. 2. Effects of ICI 170,809 as single oral doses (3, 7, 15 and 30 mg) or placebo were studied on the duration of antagonism for the ex vivo platelet aggregatory response to 5-HT and to the pupillary light constrictor response in eight healthy male volunteers. 3. Pupillary dark adapted responses to a 0.5 s light stimulus were measured using a portable infrared pupillometer, for up to 24 h after dosing. 4. The in vitro platelet 5-HT aggregation response was reduced by ICI 170,809, with depression of the dose-response curve to 5-HT at all concentrations of 5-HT and with no evidence for a parallel shift. 5. The ex vivo platelet 5-HT response demonstrated a dose related significant (P less than 0.02) decrease in aggregation reaching a maximum at 2 h after dosing with the effect persisting for at least 8 h after dosing with the 7 and 15 mg doses. 6. Resting pupil diameter (RPD), and light induced pupillary responses in the dark adapted pupil, showed a significant (P less than 0.01) dose related reduction with significant (P less than 0.05) effects still present with the 15 and 30 mg doses at 8 h after dosing. 7. We conclude that, changes in both ex vivo platelet aggregation to 5-HT and dark adapted pupil size, are significantly correlated (P less than 0.0001) with log plasma concentrations (ng ml-1) of ICI 170,809, enabling the assessment of 5-HT2-receptor antagonism in man.

Adolescent↗
PubMed1991

The effects of a 5-HT2 receptor antagonist (ICI 169,369) on changes in waking EEG, pupillary responses and state of arousal in human volunteers.

1. ICI 169,369 (2-(2-dimethylamino ethylthio)-3-phenyl quinoline) is a potent selective competitive antagonist of the 5-HT2 receptor in animal models. Effects of ICI 169,369 as single oral doses (80 and 120 mg) separated by 1 week, on the power spectrum of waking EEG, dark adapted pupil responses and sedation score, were studied in a double-blind, placebo controlled, randomised cross over within subject comparison, in six healthy male volunteers. 2. Pupillary responses were measured using a portable infrared pupillometer following 15 min dark adaptation, assessing resting vertical pupil diameter (RPD), light constricted diameter (MPD) and recovered final diameter (FPD) at the end of a 3 s measurement cycle. 3. Both doses of ICI 169,369 produced a mean 36% (range 10-54%) decrease in log 10 power of the waking EEG alpha activity with eyes closed (P less than 0.02), and mean 38% (range 2-86%) increase in theta activity at 2 h compared with placebo. 4. Both 80 and 120 mg doses of ICI 169,369 reduced RPD by approximately 30% from a predose value of 6.25 mm (+/- 0.87; 95% CI) and from placebo values 6.41 mm (+/- 1.06) and 7.48 mm (+/- 1.49) at 3 and 5 h after dosing. MPD was reduced by 50% with the 120 mg dose at 5 h after dosing (placebo 5.2 mm; ICI 169,369 2.7 mm; P less than 0.05). FPD was significantly reduced (P less than 0.01) by both doses at 3 h after dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Prevention and treatment of experimental influenza A virus infection in volunteers with a new antiviral ICI 130,685.

The initial prophylactic and therapeutic trials of ICI 130,685 against influenza A virus infection are reported. Prophylaxis with either 200 mg/day (38 volunteers received drug and 40 received placebo) or 100 mg/day (28 volunteers received drug and 28 received placebo) for seven days significantly reduced illness, mean clinical score and nasal secretion weight when volunteers were challenged with 10(4.1) EID50 of influenza virus A/Eng/40/83 (H3N2). Overall, prophylaxis with 200 mg/day and 100 mg/day gave 91% and 72% protection against illness relative to placebo, respectively. In addition, prophylaxis with both regimens for seven days also significantly reduced the number of volunteers who excreted virus. In a therapeutic study, volunteers were inoculated with the same dose of virus and those who developed symptoms which persisted for 6-15 h were treated with 200 mg/day of drug (20 volunteers) or placebo (19 volunteers) for four days. Generally, treatment reduced both the amount of virus excreted and the mean daily clinical score. However, these reductions were only statistically significant (P less than 0.05) on the third day of medication for the amount of virus excreted and on the fourth day of treatment for the mean clinical score. It was concluded that ICI 130,685 is effective in the prevention and treatment of influenza virus infection. An initial tolerance study in 16 volunteers who received either drug (200 mg/day) (8 volunteers) or placebo (8 volunteers) for seven days, indicated that the drug was generally well tolerated. Combining data from all studies, 43% of volunteers who received the drug at the 200 mg/day dosage and 21% who received placebo complained of one or more symptoms. However, symptoms were generally minor and of short duration. At the lower dosage (100 mg/day) the symptoms were qualitatively similar to those reported with placebo.

Adolescent↗
PubMed1979

Interaction of atenolol and adrenaline with respect to intraocular pressure.

1. The effects of topically administered atenolol 4% and adrenaline 1% on intraocular pressure (IOP) were investigated in fourteen healthy male human volunteers. Both the sole and combined effects of single doses of the formulations were recorded over a 7 h period. 2. Adrenaline and atenolol both produced significant reductions in IOP when compared to the placebo control, although the pattern of response differed. 3. Adrenaline had a rapid onset of action, resulting in a significant pressure reduction by 45 min post drug administration. A small upswing in IOP then occurred between 45 and 90 min, followed by a prolonged secondary reduction phase. 4. Atenolol produced a gradual reduction in IOP which reached a maximum at 180 min post drug administration and subsequently declined between 300 and 420 min. 5. Combined treatment with atenolol and adrenaline resulted in additive effects up to 180 min, and the early pressure upswing recorded with adrenaline was completely abolished. 6. The results are compatible with the hypothesis that beta 1-adrenoceptor stimulation elevates intraocular pressure. The correlation of these results with relevant animal and human pharmacological data is discussed.

Adult↗
PubMed1977

Safety of Hibitane. II. Human experience.

Chlorhexidine has been widely used in medical practice since its introduction on to the marked in the early 1950s. Primarily it has been used for topical antisepsis, e.g. pre-surgery skin preparation, burns prophylaxis, and prior to obstetrical/gynaecological procedures. This extensive experience has demonstrated the virtual absence of sensitization and a low irritancy potential for the compound. Only one significant adverse effect has been identified during medical use, namely, the production of sensorineural deafness after direct instillation into the middle ear, a property shared by several commonly used antiseptics. The encouraging reports of the use of chlorhexidine for plaque control prompted further safety investigations. It has been shown that absorption after oral ingestion is very low, and long-term oral use has not produced changes in haematological and biochemical parameters. Occasional oral intolerance of mouthrinse formulations has been reported, although no histological abnormalities were present in gingival biopsies taken after 18 months' daily use. Very occasionally, a reversible swelling of the parotid glands has been reported after use of chlorhexidine in mouthrinse formulations, but not after other methods of administration. Tooth discoloration, which shows wide inter-individual variation is seen after all dental formulations. This undesirable cosmetic effect would appear to represent the only significant argument against everyday prophylactic oral use of chlorhexidine.

Administration, Oral↗