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

• Published in: British journal of clinical pharmacology Vol. 33; no. 3; pp. 281 - 288
• Main Authors: Millson, DS, Jessup, CL, Swaisland, A, Haworth, S, Rushton, A, Harry, JD
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-03-1992; Blackwell Science
• Subjects: Adolescent; Adult; Biological and medical sciences; Double-Blind Method; Humans; Male; Medical sciences; Middle Aged; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - pharmacokinetics; Platelet Aggregation Inhibitors - pharmacology; Pupil - drug effects; Quinolines - pharmacokinetics; Quinolines - pharmacology; Reference Values; Serotonin - metabolism; Serotonin Antagonists - pharmacokinetics; Serotonin Antagonists - pharmacology; Serotoninergic system; Aggregation; Human; Platelet; Serotonin antagonist; Single dose; Oral administration; Pupillary reflex
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/j.1365-2125.1992.tb04036.x

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.