Cardiovascular and respiratory effects of dermorphin in rats.

The cardiovascular and respiratory effects of dermorphin (D) have been evaluated in freely moving or anesthetized normotensive and spontaneously hypertensive male rats. Intravenously or intracerebroventricularly administration of D produced arterial hypotension with sinus bradycardia and respiratory depression. Naloxone antagonized the effects of D. Atrial natriuretic antipeptide IgG reduced the cardiovascular responses without any significant modification of respiratory response. ICI 174864, naloxonazine and binaltorphimine did not reduce the cardiovascular and respiratory effects. In hypertensive rats D produced more intense and longer cardiovascular effects than those seen in normotensive animals. D effects involve the activation of mu and k opioid receptors for cardiovascular responses and mu 2 opioid receptors for respiratory depression without any significant effect on delta receptors. The release of atrial natriuretic peptide also appears to be involved in the cardiovascular effects of D.

Influence of rat prenatal and postnatal exposure to a non-steroidal anti-inflammatory agent (flunoxaprofen) on cardiovascular function in the progeny.

The present experiments evaluated in rats the effects of prenatal and postnatal exposure to a non-steroidal antiinflammatory agent, flunoxaprofen (5-10 and 20 mg/kg/day by the oral route), on cardiovascular function in the pups. In both conscious and anaesthetized rats pre- and postnatal flunoxaprofen exposure at the 30th and 60th day of age, significantly (P less than .05) induced a decrease of pressor response to carotid-sinus baroreceptor stimulation and to L-noradrenaline (0.1-1 and 5 micrograms/kg iv), and an increase of the hypotensive responses to L-isoprenaline (0.01-0.1 and 1 microgram/kg iv) and acetylcholine (0.01-0.1 and 1 microgram/kg iv). These effects were not observed in rats on the 90th day of age. Moreover, pre- and postnatal flunoxaprofen exposure did not modify systolic arterial blood pressure of plasma levels of catecholamines and acetylcholinesterases. Our results also show that in normotensive rats flunoxaprofen exposure during pregnancy did not affect the body weight, systolic or diastolic blood pressure or heart rate of pregnant rats. It did not affect the length of gestation, number of pups per litter or pup body weight. No macroscopic teratogenic effects were observed.

Pharmacodynamic profile of fenoverine, a novel modulator of smooth muscle motility.

Experimental research has documented that fenoverine is a depressant drug mostly active on the intestinal smooth muscle; however, it is also active on other tissues as well as on the genito-urinary tract. Fenoverine may be considered a synchronizer of smooth muscle effective in modulating the intracellular influx of calcium into the cell and its release from the intracellular pool. Fenoverine causes a reduction of the excitatory junction potential (EJP) in intestinal smooth muscle by stimulating parasympathetic efferent fibres without any change in the inhibitory junction potential (IJP). This also occurs in the presence of atropine. Fenoverine reduces the intracellular Ca2+ concentration by decreasing the calcium gradient across the cell membrane, as well as decreasing the release of Ca2+ from the intestinal pool more intensely than papaverine (but less intensely than nifedipine, verapamil or diltiazem). This phenomenon has been observed in the intestinal smooth muscle and also in the genito-urinary tract.

Aminoethers of 1,3,3-trimethyl-5-(phenylmethylene)-2-oxabicyclo[2.2.2]octan-6-h ydroxy imine with antiarrhythmic activity.

The synthesis of beta-dialkylaminoethyl ethers (III a-f) and gamma-dialkylaminopropyl ethers (III g-l) starting from 1,3,3-trimethyl-5-(phenylmethylene)-2-oxabicyclo[2.2.2]octan-6- hydroxyimine (II) is described. beta-Diisopropylaminoethyl ether (III b) and gamma-piperidinopropyl ether (III i) showed an antiarrhythmic activity in rats similar to that of quinidine. Moreover, a number of ethers (III) showed weak hypotensive and bradycardic activity in rats and moderate infiltration anesthesia in mice.

Acetic acids bearing the 1-phenyl-1H-indazole nucleus with analgesic and antiinflammatory activity.

The synthesis of [(1-phenyl-1H-indazol-4-yl)oxy]acetic acid (IV), (1-phenyl-1H-indazol-4-yl)acetic acid (IX) and (1,5,6,7)tetrahydro-1-phenyl-4H-indazol-4-iminooxy)acetic acid (XIII) starting from 1,5,6,7-tetrahydro-1-phenyl-4H-indazol-4-one (I) is described. These compounds showed a good antiinflammatory activity in rats, and an analgesic activity in mice similar or comparable to that of indomethacin.