ICI 170809, A selective 5-hydroxytryptamine antagonist, inhibits human platelet aggregation in vitro and ex vivo

Interaction between the effects of 5‐hydroxytryptamine and adrenaline on the growth of platelet thrombi in the coronary artery of the anaesthetized dog

“…Further the anti-aggregating effects of a 5-HT2 antagonist and aspirin are additive, whereas those of a cyclo-oxygenase inhibitor (aspirin) and any other drug acting on the arachidonic acid/thromboxane pathway such as a TXA2 receptor antagonist or a TXA2 synthase inhibitor are obviously not. These results allow the speculation that ICI 170809 may be of clinical use in the treatment of coronary artery thrombosis, since Blackburn et al (1990) have shown that ICI 170809 inhibits aggregation of human platelets exvivo, indicating that the effects of a specific 5-HT2 antagonist in patients with a coronary thrombosis may be similar to those suggested for ketanserin (Noble & Drake-Holland, 1990). TORR, S., NOBLE, M.I.M.…”

“…In 10 dogs cumulative intravenous doses of the selective 5-HT2 antagonist ICI 170809 (Blackburn et al, 1990) in the range 0.1-100 pg kg-' were given at O min intervals. Heart rate, arterial blood pressure and coronary blood flow were recorded throughout and measurements made 10 min after each dose.…”

Platelet 5-Hydroxytryptamine is Decreased in a Preliminary Group of Depressed Patients Receiving the 5-Hydroxytryptamine Re-Uptake Inhibiting Drug Fluoxetine

“…The 5HT, receptor antagonist ICI 170809 [14], provided by Zeneca Pharmaceuticals, Alderley Park, Macclesfield, U.K., was freshly dissolved in DMSO, protected from light and diluted with saline. The final concentration of DMSO in blood PRP (0.01%, vol./vol.)…”

“…Statistical significance: *P <0.05 compared with aspirin alone; tP<0.05 compared with aspirin and adrenaline. 14) 14.0 (7, IS)* 9.0 (6, I2)t Amitriptyline 13 (8,18) 1.6 (0, 4) 3.6 (I, 6)* 2.4 (0, 5)t P compared with control rations are required, and in vivo, where nanomolar concentrations are effective. Platelet-derived 5HT enhances platelet aggregation induced by other aggregating agents such as ADP [33] and the TXA, receptor agonist U46619 [34], but ADP and TXA, largely account for aggregation with collagen, since the contribution of 5HT to the net response is only small in vitro [16].…”

“…All patients were either being treated for affective disorders or had previously received drug treatment. The control group consisted of 13 patients (six males, seven females), median age 42 (interquartile range 36, 54) years, who had been treated with either amitriptyline, dothiepin or fluoxetine, and in each case treatment had been stopped at least 2 weeks previously [ 5 (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) weeks; median and range]. The patients treated with amitriptyline formed a second control group; this is not ideal because amitriptyline has some 5HT uptake inhibiting properties [8,91, but this group forms those with the most commonly prescribed antidepressant.…”