omega-Dialkylaminoalkyl ethers of 6-(benzyl or phenyl)-1,3,3-trimethyl-2-oxabicyclo [2.2.2]octan-6-ol with platelet antiaggregating and local anesthetic activities.

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.

[Sodium phosphocreatine and the cardiovascular and respiratory systems]. / Fosfocreatina sodica ed apparato cardiovascolare e respiratorio.

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.

Research on heterocyclic compounds. X.-Imidazo[1,2-a]pyrazine derivatives: synthesis and antiinflammatory activity.

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.

[Experimental assessment of some pharmacodynamic features of ketoprofen lysine. Pain relief activity, antipyretic effects, anti-inflammatory activity, anti-platelet aggregation activity and interference with the biosynthesis of prostaglandins]. / Analisi sperimentale di alcuni aspetti farmacodinamici del ketoprofene lisina. Attività antidolorifica, effetti antipiretici, attività anti-infiammatoria, attività antiaggregante piastrinica ed interferenze con la biosintesi delle prostaglandine.

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.

Derivatives of 5,7,7-trimethyl-6-oxa-3-azabicyclo[3.2.2]nonane with antiarrhythmic, local anesthetic and hypotensive activities. I.

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.

[Platelet aggregation and antihypertensive alpha-adrenergic agonists]. / Aggregazione delle piastrine ed anti-ipertensivi alpha-adrenergici stimolanti.

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.

[Experimental analysis of various cardiac effects of inosine]. / Analisi sperimentale di alcuni effetti cardiaci dell'inosina.

Experimental research has shown that inosine in doses of 100-500 mg/kg has a protective effect with respect to various experimentally induced myocardiopathies.

[Platelet aggregation and piribedil]. / Aggregazione delle piastrine e piribedil.

The Authors, thanks to experimental works, have established that piribedil at high concentrations inhibits ADP and thrombin aggregation effect on the rabbit PRP.