ABSTRACT
The new synthetic analogue of prostaglandin I2 (prostacyclin MM-706) influence on some hepatic function indexes was studied up in 7 dogs with an acute hepatic insufficiency caused by severe hemorrhagic shock. Rapid and steady normalization of indexes and the animals survival were promoted by intravenous infusion of MM-706 given in 300 ng/kg dose together with hemocorrector named lactoprotein given in 10 ml/kg dose (7,5 +/- 1,4) hours later. Possible action mechanisms of the MM-706 therapeutic efficacy are considered. Results of investigation performed constitute an experimental base of the MM-706 application in the complex treatment of an acute hepatic insufficiency of different genesis in the clinic.
Subject(s)
Epoprostenol/analogs & derivatives , Epoprostenol/pharmacology , Liver/drug effects , Shock, Hemorrhagic/drug therapy , Animals , Dogs , Epoprostenol/therapeutic use , Female , Liver/physiopathology , Liver Failure, Acute/drug therapy , Liver Failure, Acute/etiology , Liver Failure, Acute/physiopathology , Liver Function Tests , Male , Shock, Hemorrhagic/physiopathologyABSTRACT
The pharmacological activity of bicyclooctane and bicycloheptane analogues of prostacyclin was studied on the rat stomach muscle strip. All the analogues are partial agonists. EC50 of the most active of them, 5E isomer of bicyclooctane analogue, is 2.8.10(-7) M-1.2.10(-7) M. 5E isomers of both bicyclooctane and bicycloheptane analogues with a normal length of alpha-chain are at least by an order of values more active than the corresponding 5Z isomers. At the increase of alpha-chain by one methylene group the activity of 5E and 5Z isomers of bicycloheptane analogue becomes similar.
Subject(s)
Epoprostenol/pharmacology , Muscle, Smooth/drug effects , Prostaglandins, Synthetic/pharmacology , Animals , In Vitro Techniques , Male , Muscle Contraction/drug effects , Rats , Rats, Inbred Strains , Stereoisomerism , Stomach/drug effectsABSTRACT
E- and Z-isomers of 15-fluoro-13,14-dehydrocarbacyclin were synthesized starting from 2,3-epoxy-bicyclo[3.3.0]octan-6-one ethylene ketal with the use of 3-fluoro-1-octynydlithium.BF3 reagent and Wittig condensation. The ratio of isomeric the oxirane opening reaction and Wittig olefinization products was in each case 1:1. The synthesized compounds were identified by 13C NMR spectra. The antiaggregating activity of 5E-isomer was 2 x 10(-4) of the activity of corresponding 15-hydroxy compound, 5Z-isomer being even less active.
Subject(s)
Epoprostenol/chemical synthesis , Platelet Aggregation Inhibitors/chemical synthesis , Prostaglandins, Synthetic , Animals , Chemical Phenomena , Chemistry , Epoprostenol/pharmacology , In Vitro Techniques , Prostaglandins, Synthetic/pharmacology , RabbitsABSTRACT
Bicyclo[3.2.0]heptane analogues of prostacyclin were synthesized starting from 2,3-epoxy-bicyclo[3.2.0]heptane-6-one ethylene ketale by means of alkynydlithium-BF3-reagents and Wittig reaction. The regioselectivity of the oxirane ring opening reaction is 3:2 and stereoselectivity of Wittig olefinization is 1:1. The synthesised compounds were identified by 13C NMR spectra. The antiaggregative activity of the prostacyclin analogues on rabbit blood platelets was 10(-3)-10(-4) of the activity of PGE1, the isomers with (E)-double bond in alpha-chain being by an order more active that the (Z)-isomers. Elongation of the alpha- and omega-side chain by one carbon atom gives 2-4 fold increase of the activity. Bicyclo[3.2.0]heptane analogues of prostacyclin represent-simple and readily obtainable models for elucidation of structure-activity relationship among prostacyclin analogues.
