ABSTRACT
New nitrogen analogues of prostaglandins (11, 11a, 12, and 12a) have been synthesized starting from a 4,5-disubstituted 2-pyrrolidinone nucleus (5 and 5a) containing one side chain and a suitable functionality for elaborating the second one. These analogues had no better activity than natural prostaglandins in vitro [guinea pig ileum and trachea, rat stomach fundus strip, uterus and portal vein, ADP-induced guinea pig platelet-rich plasma (PRP) aggregation]. They similarly lacked any interesting activity in vivo [anesthetized rat blood pressure, stress, and acetylsalycilic acid (ASA) induced gastric lesions in rat].
Subject(s)
Prostaglandins, Synthetic/chemical synthesis , Animals , Chemical Phenomena , Chemistry , Guinea Pigs , In Vitro Techniques , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Platelet Aggregation/drug effects , Prostaglandins E/pharmacology , Prostaglandins, Synthetic/pharmacology , Pyrrolidinones/chemical synthesis , Pyrrolidinones/pharmacology , RatsABSTRACT
Carboprostacyclin (dl-9a-deoxy-9a-methylene-PGI2), a new stable PGI2-analogue, has been studied in vitro and in vivo. This analogue relaxes bovine coronary artery (potency ratio to PGI2 = 0.17), inhibits human PRP aggregation induced by ADP (IC50 = 12.5 nM2), deaggregates platelet clumps in cat heparinized blood (ED50 = 10.4 microgram/kg) and raises cAMP content in human PRP, but is less potent than PGI2. It is less potent (about 30 times) than PGI2 in lowering blood pressure in anaesthetized rats, inhibits basal gastric secretion in the rat and is 8 and 6 times less potent than PGE2 in protecting rat gastric mucosa from the lesions induced by stress and ASA, respectively, and about half as potent as PGE2 in protecting intestinal mucosa from damage by indomethacin.
Subject(s)
Epoprostenol/pharmacology , Prostaglandins, Synthetic/pharmacology , Prostaglandins/pharmacology , Animals , Blood Pressure/drug effects , Cats , Cattle , Cyclic AMP/blood , Gastric Mucosa/drug effects , Humans , In Vitro Techniques , Male , Muscle Relaxation/drug effects , Muscle, Smooth, Vascular/drug effects , Peptic Ulcer/prevention & control , Platelet Aggregation/drug effects , Rabbits , RatsABSTRACT
20-methyl-13,14-didehydro-PGF2 alpha has been assayed for antagonistic activity against PGF2 alpha and PGE2 on different smooth msucle preparations in vitro. This compound may be considered a selective and probably a competitive antagonist of PGF2 alpha on rat uterus in vitro.
Subject(s)
Dinoprost/analogs & derivatives , Muscle Contraction/drug effects , Prostaglandin Antagonists , Prostaglandins F, Synthetic/pharmacology , Animals , Female , In Vitro Techniques , Muscle, Smooth/drug effects , Prostaglandins F/antagonists & inhibitors , Rats , Uterus/drug effectsABSTRACT
Harmaline, an alcaloid of Paganum Armala, induces tremors of central origin and increases cerebellar cGMP without affecting cortical and cerebellar prostaglandin levels. 16(S)-16-methyl PGE2 protects the animals against the seizures induced by the alcaloid and prevents the concomitant rise in cerebellar cGMP. Experiment performed in cats and limited to pharmacological observations, confirmed that, the PGE2 derivative, is a powerful antitremorogenic agent at doses that are devoid of appreciable side effects.
Subject(s)
Alkaloids/antagonists & inhibitors , Brain/metabolism , Harmaline/antagonists & inhibitors , Nucleotides, Cyclic/metabolism , Prostaglandins E, Synthetic/pharmacology , Prostaglandins/metabolism , Tremor/physiopathology , Animals , Brain/drug effects , Cats , Cerebellum/metabolism , Cerebral Cortex/metabolism , Male , Prostaglandins E/metabolism , Prostaglandins F/metabolism , Rats , Tremor/chemically induced , Tremor/metabolismSubject(s)
Endorphins/pharmacology , Enkephalins/pharmacology , Morphine/pharmacology , Adenylyl Cyclases/metabolism , Analgesics , Animals , Corpus Striatum/enzymology , Genotype , In Vitro Techniques , Male , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Motor Activity/drug effects , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Reaction Time/drug effects , Species Specificity , Vas Deferens/drug effectsABSTRACT
The horse-chestnut saponin Aescin, an anti-exudative compound, induces contraction of isolated portal vein of rat and rabbit. This effect appears to be mediated by Prostaglandins of Falpha type. The ability of Aescin to stimulate generation and release of Prostaglandins has been demonstrated in isolated lung of the rat. Mass-fragmentographic analysis of the lung effluent indicate that when Aescin is perfused through this organ the release of PGF2alpha is increased. The capability of Aescin to generate Prostaglandins is discussed in connection with its anti-exudative activity.
Subject(s)
Escin/pharmacology , Prostaglandins F/metabolism , Saponins/pharmacology , Animals , Lung/metabolism , Male , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Perfusion , Portal Vein/drug effects , Rabbits , Rats , Rats, Inbred Strains , Secretory Rate/drug effectsABSTRACT
Fully convulsant doses of pentamethylenetetrazole cause marked increase in rat brain cortical PGF2alpha, PGE2, cGMP and cAMP during seizures, whereas subconvulsant doses cause an increase of rat brain cortical PGF2alpha without affecting the other biochemical parameters considered. Rat cerebellar prostaglandins were not modified by the convulsant agent at either dosage.
