ABSTRACT
The synthesis of 1,3,3-trimethyl-6-phenyl-2-oxabicyclo[2.2.2]octan-6-ol 2 and 6-benzyl-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-ol 3 starting from (+)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-one and phenylmagnesium bromide or benzylmagnesium chloride, respectively, is described. Alcohols 2 and 3 gave a series of omega-dialkylaminoalkyl ethers 4 by reaction as sodium salts with omega-chloroalkyldialkylamines in toluene solution. Some compounds 4, in particular those derived from alcohol 2, showed a strong platelet antiaggregating activity in vitro, superior to that of acetylsalicylic acid, as well as in general an appreciable local anesthetic activity and a weak sedative effect in mice.
Subject(s)
Anesthetics, Local/chemical synthesis , Bridged Bicyclo Compounds/chemical synthesis , Platelet Aggregation Inhibitors/chemical synthesis , Anesthesia , Anesthetics, Local/pharmacology , Animals , Blood Pressure/drug effects , Bridged Bicyclo Compounds/pharmacology , Chloroform , Humans , In Vitro Techniques , Magnetic Resonance Spectroscopy , Mice , Motor Activity/drug effects , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/pharmacology , Rats , Spectrophotometry, Infrared , Ventricular Fibrillation/chemically induced , Ventricular Fibrillation/prevention & controlSubject(s)
Muscles/drug effects , Pyridinium Compounds/pharmacology , Animals , Dogs , Female , Guinea Pigs , Heart/drug effects , Intestines/drug effects , Muscle, Smooth/drug effects , Ranidae , Rats , Receptors, Muscarinic/drug effects , Receptors, Nicotinic/drug effects , Ureter/drug effects , Uterus/drug effectsSubject(s)
Anti-Inflammatory Agents/chemical synthesis , Imidazoles/chemical synthesis , Analgesics/chemical synthesis , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Imidazoles/pharmacology , Magnetic Resonance Spectroscopy , Pyridines/chemical synthesis , Pyridines/pharmacology , Pyrimidines/chemical synthesis , Pyrimidines/pharmacology , Rats , Spectrophotometry, Infrared , Stomach Ulcer/drug therapy , Thiazoles/chemical synthesis , Thiazoles/pharmacologyABSTRACT
In the dog, rat and chick, phosphocreatine-Na has not caused, from an experimental point of view, significative modifications of the cardiovascular- and respiratory-apparatus, of the reactivity of the cardio-regulator centers, of the baroreceptorial carotid-sinus and glomus reactivity, of the gangliar-, muscarinic-, histaminergic-, dopaminergic-, beta-adrenergic- and serotoninergic- vasomotor reactivity; only the vasomotor reactivity of a constrictive-type induced by epinephrine, nor-epinephrine, occlusion of the two common carotid arteries, hypertension and by BaCl2 is moderately reduced. It is interesting to note that the hypotensive response evoked by adenosine was augmented.
Subject(s)
Cardiovascular System/drug effects , Phosphocreatine/pharmacology , Respiratory System/drug effects , Animals , Blood Pressure/drug effects , Chickens , Dogs , Electrocardiography , Heart Rate/drug effects , Pulmonary Circulation/drug effects , RatsSubject(s)
Anesthetics, Local/chemical synthesis , Anti-Arrhythmia Agents/chemical synthesis , Antihypertensive Agents/chemical synthesis , Bridged Bicyclo Compounds, Heterocyclic , Bridged Bicyclo Compounds/chemical synthesis , Bridged-Ring Compounds/chemical synthesis , Acetylcholine/antagonists & inhibitors , Animals , Bridged Bicyclo Compounds/pharmacology , Chemical Phenomena , Chemistry , Epinephrine/toxicity , Guinea Pigs , Hemodynamics/drug effects , Mice , RabbitsSubject(s)
6-Ketoprostaglandin F1 alpha/pharmacology , Carboprost/pharmacology , Epoprostenol/pharmacology , Platelet Aggregation/drug effects , Prostaglandins F, Synthetic/pharmacology , Prostaglandins F/pharmacology , Prostaglandins/pharmacology , Adenosine Diphosphate/pharmacology , Animals , Rabbits , Thrombin/pharmacologyABSTRACT
Since we had previously observed the considerable anti-inflammatory activity of imidazo[1,2-a]pyrazine 2-acetic acid, we prepared a series of imidazo[1,2-a]pyrazine derivatives, bearing some substituents on the pyrazine ring and a carboxylic, acetic or alpha-methylacetic moiety on the imidazole ring. These new compounds were tested for antiinflammatory, analgesic, antipyretic and ulcerogenic activities.
Subject(s)
Anti-Inflammatory Agents/chemical synthesis , Pyrazines/chemical synthesis , Analgesics/chemical synthesis , Animals , Anti-Inflammatory Agents/toxicity , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Mice , Pyrazines/pharmacology , Pyrazines/toxicity , Rats , Stomach Ulcer/chemically inducedABSTRACT
An experimental assessment was made of the analgesic, anti-inflammatory and platelet anticlumping activity of ketoprophene lysine, and its effect on body temperature and prostaglandin synthesis. The drug's pharmacodynamics was very similar to that of ketoprophene and its gastric tolerance was better. It was also well tolerated by the dog joint surfaces and cardiovascular apparatus when given i.m. or i.v., even at doses higher than those advised for man, or when infiltrated in ketoreceptor areas.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Ketoprofen/pharmacology , Lysine/analogs & derivatives , Phenylpropionates/pharmacology , Platelet Aggregation/drug effects , Prostaglandins/biosynthesis , Animals , Body Temperature/drug effects , Dogs , Female , Ketoprofen/analogs & derivatives , Lysine/pharmacology , Male , Malondialdehyde/metabolism , Mice , Rabbits , RatsABSTRACT
The synthesis of three series of 3-acyl-, 3-alkyl- and 3-dialkylaminoacetyl-5,7,7-trimethyl-6-oxa-3-azabicyclo[3.2.2]nonanes, (III), (IV) and (V), respectively, is described. A number of these compounds showed surface anesthesia in rabbits and infiltration anesthesia in mice, and antiarrhythmic activity in guinea pigs and mice, all effects being superior or similar to those of lidocaine. The circulatory, cardiac and respiratory effects in dogs and hens are also described.
Subject(s)
Anesthetics, Local/chemical synthesis , Anti-Arrhythmia Agents/chemical synthesis , Antihypertensive Agents/chemical synthesis , Bridged Bicyclo Compounds/chemical synthesis , Bridged-Ring Compounds/chemical synthesis , Animals , Chemical Phenomena , Chemistry , Chickens , Female , Guinea Pigs , Hemodynamics/drug effects , Male , Mice , RabbitsABSTRACT
In their experimental researches the Authors showed that the well-known antihypertensive alpha-adrenergic stimulant drugs (clonidine, flutonidine and guanabenz) were able to antagonize at very high concentrations the platelet aggregation induced by ADP and by thrombin on rabbit PRP.
Subject(s)
Adrenergic alpha-Agonists/pharmacology , Clonidine/pharmacology , Guanabenz/pharmacology , Guanidines/pharmacology , Imidazoles/pharmacology , Platelet Aggregation/drug effects , Adenosine Diphosphate/antagonists & inhibitors , Animals , Rabbits , Thrombin/antagonists & inhibitors , Toluidines/pharmacologyABSTRACT
Experimental research has shown that inosine in doses of 100-500 mg/kg has a protective effect with respect to various experimentally induced myocardiopathies.
Subject(s)
Heart/drug effects , Inosine/pharmacology , Alanine Transaminase/analysis , Animals , Aspartate Aminotransferases/analysis , Columbidae , Creatine Kinase/analysis , Electrocardiography , Emetine/pharmacology , Guinea Pigs , Isoproterenol/pharmacology , L-Lactate Dehydrogenase/analysis , Male , Mice , Myocardium/analysis , Organ Size/drug effects , Rats , Thyroxine/pharmacologyABSTRACT
The Authors, thanks to experimental works, have established that piribedil at high concentrations inhibits ADP and thrombin aggregation effect on the rabbit PRP.