Acute reduction of TxA2 platelet binding sites after in vivo administration of a TxA2 receptor inhibitor

Br J Clin Pharmacol. 1991 Apr;31(4):439-43. doi: 10.1111/j.1365-2125.1991.tb05560.x.

Abstract

1. Picotamide has been shown to interfere competitively with the thromboxane A2 (TxA2) platelet receptor. In the present study the effect of in vivo administration of picotamide on TxA2 human platelet receptors was investigated in 10 healthy subjects. 2. Picotamide (300 mg x 3 daily) or placebo were administered in a double-blind, cross-over, placebo controlled study, each treatment lasting 1 week with a 2 week interval period. TxA2 receptors were investigated by a direct radioligand binding assay method employing [125I]-PTA-OH as labelled ligand. Platelet studies were performed on the first day of treatment immediately before and 2, 4 and 8 h after the ingestion of the drug. The effects of chronic administration were assessed on the seventh day. 3. Two and 4 h after the administration of picotamide 300 mg orally platelet TxA2 receptors were significantly reduced from 1366 +/- 237 to 957 +/- 221 (P less than 0.05) and 753 +/- 119 receptors/platelet (mean +/- s.d.) (P less than 0.03). After 8 h platelet receptor population was restored (1362 +/- 324, NS). The same pattern was observed after 7 days of treatment. Thus picotamide seems to induce a short lasting down regulation of platelet TxA2 receptors.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Binding Sites
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Down-Regulation
  • Humans
  • Middle Aged
  • Phthalic Acids / pharmacology*
  • Receptors, Prostaglandin / analysis
  • Receptors, Prostaglandin / drug effects*
  • Receptors, Thromboxane
  • Thromboxane A2 / metabolism*

Substances

  • Phthalic Acids
  • Receptors, Prostaglandin
  • Receptors, Thromboxane
  • Thromboxane A2
  • picotamide