2-(6-Carboxyhexyl)-3-n-hexylcyclohexylamine (IBI P-05006) is a molecule with cytoprotective and antisecretory actions. Since its chemical structure resembles that of the prostanoid nucleus of thromboxane (Tx) A2, the possibility of antiplatelet activity was investigated. The aims of our study were to evaluate a possible inhibitory effect of IBI P-05006 on in vitro platelet aggregation induced by different stimuli and to characterize its mechanism of action. For this purpose, selected mechanisms of platelet function were evaluated. IBI P-05006 inhibited platelet aggregation induced by arachidonic acid or U46619, at concentrations ranging from 0.4 to 4 microM, dose dependently, without interfering with arachidonic acid metabolism. The possibility that the compound acts through adenylate cyclase stimulation was ruled out by measurement of cAMP levels, which were not increased. Receptor binding studies indicated competitive inhibition by IBI P-05006 of the binding of the ligand [3H]SQ29548 to the TxA2/(prostaglandin) PG-cyclic endoperoxides receptor with IC50 in the range of concentrations active on platelet aggregation. In conclusion, IBI P-05006 inhibits in vitro human platelet aggregation through a specific mechanism of competition for the TxA2/PG-cyclic endoperoxides receptor.

01 Apr 1992·European Journal of Drug Metabolism and PharmacokineticsQ4 · MEDICINE

Mass spectrometric identification of urinary and plasma metabolites of 2-(6’-carboxyhexyl)-3-n-hexylcyclohexylamine, a new antiaggregating agent

Q4 · MEDICINE

Article

Author: R. Caponi ; P. Farina ; R. Fanelli ; E. Bosone ; E. Benfenati

The compound IBI-P-05006, 2-(6'-carboxyhexyl)-3-n-hexylcyclohexylamine, is an antiaggregating agent under development. IBI-P-05006 is an in vitro inhibitor of platelet aggregation. The biotransformation of this compound has been studied in the dog and rat. We present here a study on the metabolites of IBI-P-05006 found in dog and rat urine, and in dog plasma. Analyses were done by gas chromatography-mass spectrometry. In dog urine 15 metabolites were identified. Some of them were also found in dog plasma and in rat urine. The unmetabolized drug was found only in plasma. 10 different hydroxylated metabolites were characterized. The hydroxyl groups were introduced in the hexyl chain in positions omega-4, omega-3, omega-2, omega-1 and omega.

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Indication	Highest Phase	Country/Location	Organization	Date
Thrombosis	Preclinical	IT	Istituto Biochimico Italiano Giovanni Lorenzini SpA	-

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