Disease relevance of [(2R,5S)-2,5-dimethyl-5-(octadecylcarbamoyloxymethyl)oxolan-2-yl]methoxy-(2-quinolin-1-ylethoxy)phosphinic acid

• In addition, SDZ 63-675 and WEB 2170 prevented early transient bradycardia and hypotension and reduced the infarct size, judged by staining with tetrazolium at 2 and 24 hours after reperfusion, and by histological examination at 24 hours [1].
• The administration of two structurally unrelated platelet-activating factor-receptor antagonists (SDZ 63-675, 5 mg/kg body weight, and WEB 2170, 5 mg/kg body weight) before reperfusion significantly reduced the accumulation of PMN, as well as the hemodynamic alterations and the size of necrotic area [1].
• Escherichia coli endotoxin (055-B5) was infused intravenously into anesthetized young pigs at 5 micrograms/kg the first hour, followed by 2 micrograms/kg/hour for 3 hours in the presence and absence of SRI 63-675, a specific PAF receptor antagonist [2].
• Animals pretreated with SRI 63-675 showed a similar degree of polycythemia after 1 h, but thereafter hematocrit fell and was not different from sham-burned animals [3].
• Bolus injection of SRI 63-675 at the time of Ps infusion blocked the early pulmonary hypertension, attenuated the early and late fall in PaO2, ameliorated the increase in EVLW, and prevented the late (150-180 min) increase in albumin flux [4].

High impact information on [(2R,5S)-2,5-dimethyl-5-(octadecylcarbamoyloxymethyl)oxolan-2-yl]methoxy-(2-quinolin-1-ylethoxy)phosphinic acid

• In vitro and in vivo pharmacological profiles of the PAF receptor antagonist SRI 63-675 [5].
• The ratio (1:6) in the primate of PAF used (6.3 nmol kg-1) to antagonist at the ED50 (40.7 nmol kg-1) indicates exceptional potency of SRI 63-675 in this species [5].
• Platelet activation by purified PAF and by sperm phospholipid fractions was inhibited by the receptor antagonist SRI 63-675 [6].
• 2. Intradermal injection of two antagonists structurally-related to Paf (SRI 63-675 and CV-3988) resulted in a partial inhibition of Paf-induced oedema formation but at high doses of antagonist, marked agonist activities were detected [7].
• Animals were fasted overnight, anesthetized with pentobarbital, and then injected with saline or the PAF antagonist SRI 63-675 prior to a 25% body surface area scald injury [3].

Chemical compound and disease context of [(2R,5S)-2,5-dimethyl-5-(octadecylcarbamoyloxymethyl)oxolan-2-yl]methoxy-(2-quinolin-1-ylethoxy)phosphinic acid

• In normal Wistar rats, SDZ 63-675 (1.2 mg/kg) inhibited hypotension and hemoconcentration induced by PAF-acether (0.2-0.8 micrograms/kg.min) [8].
• The endotoxin-induced pulmonary hypertension, decreased cardiac index, and increases in pulmonary vascular resistance and alveolar-arterial O2 gradient were attenuated by SRI 63-675 [9].

Biological context of [(2R,5S)-2,5-dimethyl-5-(octadecylcarbamoyloxymethyl)oxolan-2-yl]methoxy-(2-quinolin-1-ylethoxy)phosphinic acid

• In the rat SRI 63-675 inhibited 0.1 microgram kg-1 i.v. PAF-induced hypotension, with an ED50 of 32 micrograms kg-1 i.v. Using the same PAF challenge in the guinea pig, SRI 63-675 inhibited the hemoconcentration (ED50 = 17 micrograms kg-1 i.v.) and bronchoconstriction (ED50 = 24 micrograms kg-1 i.v.) responses [5].
• Sole administration of SRI 63-675 induced rapid and transient changes in peripheral blood cell counts, and blood pressure and heart rate suggestive of intrinsic PAF-like activity [10].

Anatomical context of [(2R,5S)-2,5-dimethyl-5-(octadecylcarbamoyloxymethyl)oxolan-2-yl]methoxy-(2-quinolin-1-ylethoxy)phosphinic acid

• The PAF receptor antagonist BN 52021 did not block the PAF effects in this system, and the PAF receptor antagonist SRI 63-675 caused a dose dependent inhibition of T cell subset proliferation [11].

Associations of [(2R,5S)-2,5-dimethyl-5-(octadecylcarbamoyloxymethyl)oxolan-2-yl]methoxy-(2-quinolin-1-ylethoxy)phosphinic acid with other chemical compounds

• L-659,989 (2 or 10 mg/kg iv) and SDZ 63-675 (5 mg/kg iv) abolished the vasoconstrictor response but not the postcapillary venular permeability response to PAF [12].

Gene context of [(2R,5S)-2,5-dimethyl-5-(octadecylcarbamoyloxymethyl)oxolan-2-yl]methoxy-(2-quinolin-1-ylethoxy)phosphinic acid

• Concomitant administration of the PAF receptor antagonist SRI 63-675 in a dose of 50 micrograms/kg/min completely reversed the effects of PAF [13].

Analytical, diagnostic and therapeutic context of [(2R,5S)-2,5-dimethyl-5-(octadecylcarbamoyloxymethyl)oxolan-2-yl]methoxy-(2-quinolin-1-ylethoxy)phosphinic acid

• Two hours after reperfusion, the percentage of increase of 111In-labeled PMN in transmural central ischemic zone was significantly reduced in rabbits pretreated with SDZ 63-675 (51.4 +/- 7.9) or WEB 2170 (32.4 +/- 8.8) with respect to untreated rabbits (107.6 +/- 13.5) [1].
• In sensitized rats, SDZ 63-675 (1.2 mg/kg) increased the survival rate, reduced the vascular collapse and suppressed the hemoconcentration induced by intravenous injection of the antigen [8].
• Bioassay of RP-HPLC fractions that were derived from endotoxemic blood and that eluted at a retention time consistent with [3H]alkyl PAF caused aggregation of washed rabbit platelets that was inhibited by SRI 63-675 [9].

References