Pharmacological profile of a novel potent and specific PAF receptor antagonist, the 59227 RP

Robaut, C.; Mondot, S.; Floch, Anne; Tahraoui, L.; Cavero, Icilio

doi:10.1016/0090-6980(88)90239-0

Cited by 11 publications

(1 citation statement)

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“…In contrast, as already discussed for PAF, collagen activityincreased slightly under these experimental conditions. RP 59227 (Robaut et al, 1988;Marquis et al, 1989), WEB 2086 (Casals-Stenzel et al, 1981) and (Terashita et al, 1987) caused parallel displacements of the PAF log concentration-response curve without depressing the maximum response to PAF, in all the preparations of platelets used in this study. However, the potency of these antagonists was influenced by the medium in which platelets were suspended.…”

Section: Discussionmentioning

confidence: 96%

Influence of plasma protein content and platelet number on the potency of PAF and its antagonist RP 59227 in rabbit platelet preparations

Floch¹,

Cavero²

1990

British J Pharmacology

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The potency of platelet activating factor (PAF) as a pro‐aggregatory agent and of RP 59227, a selective antagonist of PAF‐induced platelet aggregation, was determined in several types of rabbit platelet preparations. PAF produced concentration‐dependent responses irrespective of whether the suspension medium for the platelets (200,000 per μl) was undiluted plasma (PRP), saline‐diluted plasma (dil. PRP) or a salt solution (WP: washed platelets). The potency of PAF, expressed as pD2, was 3 fold higher in WP than PRP or diluted PRP (dil. PRP) for which the ratio (v/v) of total plasma to saline was 1:1.5. In PRP and WP preparations, an increase in the number of platelets in the reaction medium from 200,000 to 600,000 enhanced the potency of PAF slightly (2.3 fold). Furthermore, PAF was 3 times more potent in WP than PRP when studied in preparations containing either 200,000, 400,000 or 600,000 platelets per μl. RP 59227, like the reference compounds WEB 2086 and CV‐6209, behaved as a competitive antagonist against PAF‐evoked platelet aggregation in PRP, WP and dil. PRP (200,000 platelets per μl). Their potency was slightly greater (1.6 to 2.6 fold more) in dil. PRP than in WP, but in PRP it was 3.5 to 4.3 times lower than in WP. RP 59227 was 2.3 and 5.0 times less potent when the platelet number of the PRP suspension was increased from 200,000 to 400,000 and 600,000 per μl, respectively, whereas the potency of RP 59227 in WP was not modified by these changes in platelet number. Furthermore, CV‐6209, RP 59227 and WEB 2086 were found to be 2.8 to 3.3 times more potent when studied after 10 rather than 1 min incubation time. In conclusion, methodological variables such as platelet number, plasma protein content and incubation time can modify the potency not only of PAF, as an aggregatory agent, but also of its antagonists. Thus, only platelet aggregation studies carried out by using well‐defined experimental conditions afford an appropriate investigational approach to establish a potency rank order for PAF‐receptor antagonists. Furthermore, dil. PRP which can be easily and rapidly prepared appears to be as appropriate as WP to determine pA2 values for PAF antagonists.

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Section: Discussionmentioning

confidence: 96%