Platelet aggregation inhibitory activity and vasodepressor activity of a series of bicyclo[3.2.0]hetp-6-ylidene iminoxy alkanoic acids with modified lower side chains |
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| Authors: | Counde O-Yang Helen Y Wu Denis J Kertesz Arthur F Kluge Marshall B Wallach Anthony L Willis Donald L Smith Li-Feng K Chang |
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| Institution: | 1. Platelet Proteomics Group, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidad de Santiago de Compostela, Instituto de Investigación Sanitaria (IDIS), Santiago de Compostela, Spain;2. CSIC/UAB Proteomics Laboratory, IIBB-CSIC-IDIBAPS, Barcelona, Spain;3. Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany |
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| Abstract: | Prostacyclin analogues derived from modification of the lower side chain of the bicyclo3.2.0]hept-6-ylidene iminoxyacetic acid (
) were studied in inhibition of
and
platelet aggregation and in the spontaneously hypertensive rat. Iminoxyacetic acids (
) and iminoxypropionic acid
) were 2.9, 3.0, 1.9 and 2.0 times respectively more potent than PGE1 in inhibiting ADP-induced aggregation of human platelets
. Following intravenous administration at a dose of 90–110 μg/kg in the guinea pig, iminoxyacetic acids (
), (
) and iminoxypropionic acid (
) showed a maximum inhibition of 82–92% with a half life in the range of 14–22 min. Following oral administration at a dose of 1 mg/kg in the guinea pig, iminoxyacetic acids (
) and (
) inhibited heterologous platelet aggregation for 4.5 h. Following intravenous administration in spontaneously hypertensive rats, acids
)-(
) lowered the mean blood pressure in a dose dependent manner. At a dose of 100 μg/kg, the effect lasted for 20–40 min. |
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