cicaprost and acetylsalicylic-acid-lysinate

The antithrombotic effects of the stable PGI2-analogue Cicaprost, acetylsalicylic acid (Aspisol), the low molecular weight heparin CY 216 (Fraxiparin) and Molsidomin (Corvaton) have been investigated alone and in combinations in a thrombosis model in rats in which mesenteric venules with a diameter of 20-30 microns were injured by defined argon laser lesions. In this animal thrombosis model all agents showed a significant and dose-dependent antithrombotic effect. A strong additive effect was observed when Cicaprost was infused together with an i.v. dose of 0.1 mg/kg Molsidomin. A similar additive effect was observed after infusion of minimal effective doses of Cicaprost together with Fraxiparin. The combination of Cicaprost and Aspisol did not have any additive effect. Our results suggest that combinations of antithrombotic agents which show additive effects in animal thrombosis model may lead to a more effective prophylaxis and treatment of human venous or arterial thrombosis.

Topics: Animals; Aspirin; Drug Synergism; Drug Therapy, Combination; Epoprostenol; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Lysine; Male; Molsidomine; Rats; Rats, Inbred Strains; Thrombosis

The antithrombotic effect of a thromboxane A2 receptor antagonist (HN-11501:5-[2-(4-chlorophenylsulfonylamino)-ethyl]-2-thienylox y-acetic acid) alone and in combination with other antithrombotic agents has been studied in an experimental thrombosis model in which laser lesions are used to induce a defined thrombosis in rat mesenteric venules. The thromboxane receptor antagonist showed a significant and dose-dependent antithrombotic effect if given orally. The strongest additive thrombosis-inhibiting effect was observed after oral administration of HN-11501 at a dose of 2.5 mg/kg together with an intravenous infusion of 1 microgram/kg/h of a prostacyclin analogue (cicaprost). An additive antithrombotic effect was also observed after oral application of 2.5 mg/kg of HN-11501 and intravenous injection of 0.2 mg/kg of a low molecular weight heparin (Fraxiparine). The combination of 2.5 mg/kg of HN-11501 orally with an intravenous injection of 0.1 mg/kg molsidomine also had a significant additive effect. No significant additive effect was observed when 2.5 mg/kg of HN-11501 and 10 mg/kg of acetylsalicylic acid were orally administered simultaneously.

Topics: Animals; Aspirin; Drug Synergism; Epoprostenol; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Lasers; Lysine; Male; Microcirculation; Molsidomine; Rats; Rats, Wistar; Receptors, Thromboxane; Sulfonamides; Thiophenes; Thrombophlebitis; Venules

1. The effects of paracetamol and lysine acetylsalicylate (L-AS) on high-threshold mechanonociceptors have been investigated by recording neural activity from the inflamed ankle joint in anaesthetized rats with mild adjuvant-induced monoarthritis. 2. Paracetamol (50 mg kg-1, i.v.) and L-AS (100 mg kg-1, i.v., equivalent to 50 mg kg-1 aspirin) both caused a maximal reduction of about 40% in mechanically-evoked discharge and of 30% in ongoing (spontaneous) activity by about 15 min after the injection: a second dose of either drug did not have any significant additional effect on discharge. 3. The prostanoid IP receptor agonist, cicaprost (0.1-0.5 micrograms), increased both mechanically-evoked and ongoing discharge to pre-paracetamol levels when injected close-arterially 30-50 min after paracetamol, whereas prostaglandin E2 (PGE2) was relatively ineffective at restoring activity. 4. The results suggest that prostacyclin (PGI2) contributes to the sensitization of high-threshold joint mechanonociceptors in adjuvant-induced monoarthritis, and that paracetamol and L-AS both act to reduce discharge by inhibiting the synthesis of prostacyclin in the joint capsule. 5. Paracetamol has a direct peripheral action affecting joint capsule mechanonociceptors in rat adjuvant-induced arthritis which is very similar to that of the soluble aspirin preparation, L-AS. These findings, together with the existing literature concerning the anti-arthritic effects of paracetamol, are relevant to the treatment of chronic inflammatory disorders such as rheumatoid arthritis.

Topics: Acetaminophen; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Aspirin; Epoprostenol; Lysine; Male; Mechanoreceptors; Neural Conduction; Neurons; Nociceptors; Pain; Rats; Rats, Inbred Strains; Salicylates; Sensory Thresholds; Tarsus, Animal