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Biological effects of the new platelet-activating factor receptor antagonist (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride.
Arzneimittelforschung. 1994 Mar; 44(3):317-22.A

Abstract

SM-12502 ((+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one HCl, CAS 119383-00-5) inhibited platelet-activating factor (PAF)-induced aggregation of rabbit and human platelets with IC50 values of 2.3 mumol/l and 4.7 mumol/l, respectively, but did not inhibit platelet aggregation induced by adenosine diphosphate, collagen, thrombin, arachidonic acid, U46619 (a thromboxane A2 agonist) or Ca2+ ionophore A23187 at concentrations up to 400 mumol/l. SM-12502 competitively antagonized 3H-PAF binding to rabbit platelets with an IC50 of 1.0 mumol/l. In contrast, the anti-PAF activity of the optical isomer SM-12501 ((-)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one HCl) was much weaker and its IC50 was more than 100 mumol/l. SM-12502 prevented PAF-induced death in mice with ID50 values of 4.8 mg/kg (i.v.) or 68.6 mg/kg (p.o.). In guinea pigs, SM-12502 inhibited PAF (0.1 micrograms/kg)-induced hemoconcentration with ID50 values of 1.9 mg/kg (i.v.) or 40.2 mg/kg (p.o.). In addition, SM-12502 inhibited PAF (10 ng/kg)-induced hypotension in rats with ID50 values of 2.0 mg/kg (i.v.) or 6.5 mg/kg (p.o.). The in vivo effects of SM-12501 were much weaker. Orally administered SM-12502 showed rapid absorption and a long duration of pharmacological activity in rats. SM-12502 afforded dose-dependent protection against anaphylactic death in mice with ID50 values of 18.4 mg/kg (i.v.) and 136 mg/kg (p.o.). It also inhibited endotoxin (E. coli 0.55:B5, 60 mg/kg)-induced death in mice, with ID50 values of 119 mg/kg (i.v.) and 182 mg/kg (p.o.).(

ABSTRACT

TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Research Laboratories, Sumitomto Pharmaceuticals Co., Ltd., Osaka, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8192697

Citation

Imanishi, N, et al. "Biological Effects of the New Platelet-activating Factor Receptor Antagonist (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one Hydrochloride." Arzneimittel-Forschung, vol. 44, no. 3, 1994, pp. 317-22.
Imanishi N, Murakami-Uchida M, Koike H, et al. Biological effects of the new platelet-activating factor receptor antagonist (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride. Arzneimittelforschung. 1994;44(3):317-22.
Imanishi, N., Murakami-Uchida, M., Koike, H., Natsume, Y., & Morooka, S. (1994). Biological effects of the new platelet-activating factor receptor antagonist (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride. Arzneimittel-Forschung, 44(3), 317-22.
Imanishi N, et al. Biological Effects of the New Platelet-activating Factor Receptor Antagonist (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one Hydrochloride. Arzneimittelforschung. 1994;44(3):317-22. PubMed PMID: 8192697.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Biological effects of the new platelet-activating factor receptor antagonist (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride. AU - Imanishi,N, AU - Murakami-Uchida,M, AU - Koike,H, AU - Natsume,Y, AU - Morooka,S, PY - 1994/3/1/pubmed PY - 1994/3/1/medline PY - 1994/3/1/entrez SP - 317 EP - 22 JF - Arzneimittel-Forschung JO - Arzneimittelforschung VL - 44 IS - 3 N2 - SM-12502 ((+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one HCl, CAS 119383-00-5) inhibited platelet-activating factor (PAF)-induced aggregation of rabbit and human platelets with IC50 values of 2.3 mumol/l and 4.7 mumol/l, respectively, but did not inhibit platelet aggregation induced by adenosine diphosphate, collagen, thrombin, arachidonic acid, U46619 (a thromboxane A2 agonist) or Ca2+ ionophore A23187 at concentrations up to 400 mumol/l. SM-12502 competitively antagonized 3H-PAF binding to rabbit platelets with an IC50 of 1.0 mumol/l. In contrast, the anti-PAF activity of the optical isomer SM-12501 ((-)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one HCl) was much weaker and its IC50 was more than 100 mumol/l. SM-12502 prevented PAF-induced death in mice with ID50 values of 4.8 mg/kg (i.v.) or 68.6 mg/kg (p.o.). In guinea pigs, SM-12502 inhibited PAF (0.1 micrograms/kg)-induced hemoconcentration with ID50 values of 1.9 mg/kg (i.v.) or 40.2 mg/kg (p.o.). In addition, SM-12502 inhibited PAF (10 ng/kg)-induced hypotension in rats with ID50 values of 2.0 mg/kg (i.v.) or 6.5 mg/kg (p.o.). The in vivo effects of SM-12501 were much weaker. Orally administered SM-12502 showed rapid absorption and a long duration of pharmacological activity in rats. SM-12502 afforded dose-dependent protection against anaphylactic death in mice with ID50 values of 18.4 mg/kg (i.v.) and 136 mg/kg (p.o.). It also inhibited endotoxin (E. coli 0.55:B5, 60 mg/kg)-induced death in mice, with ID50 values of 119 mg/kg (i.v.) and 182 mg/kg (p.o.).(ABSTRACT TRUNCATED AT 250 WORDS) SN - 0004-4172 UR - https://www.unboundmedicine.com/medline/citation/8192697/Biological_effects_of_the_new_platelet_activating_factor_receptor_antagonist__+__cis_35_dimethyl_2__3_pyridyl_thiazolidin_4_one_hydrochloride_ DB - PRIME DP - Unbound Medicine ER -