Evidence for catecholamine-depleting action of fluoxetine.

The present investigation was undertaken to study the interaction of fluoxetine with 5-hydroxytryptamine (5-HT) and noradrenaline (NA) in rat anococcygeus muscle and vas-deferens. In rat anococcygeus muscle responses to NA were significantly potentiated after 30 min and 60 min incubation with fluoxetine (2.9 x 10(-9) M). The responses to 5-HT were however, inhibited after 30 min incubation with fluoxetine in this preparation. On rat vas-deferens also, the responses to NA were potentiated after 30 min incubation with fluoxetine. The response to 5-HT were not altered significantly. In rats pretreated with fluoxetine (5 mg/kg, ip) for seven days, the responses to NA were significantly potentiated in rat anococcygeus muscle. Whereas the responses to 5-HT and tyramine were significantly inhibited. The inhibited responses to 5-HT restored back to normal when the anococcygeus muscle was pre-incubated with NA for 30 min.

Magnesium and reserpine influence norepinephrine sensitivity of vas deferens in rats.

Reserpine induced supersensitivity to norepinephrine (NE) in rat vas deferens was sought by alteration of Mg++ and Ca++ concentration in incubation medium in the absence and presence of EDTA. Vas deferens incubated in Mg++ free and Mg++ excess media showed supersensitivity and subsensivity to NE respectively. Alterations in the sensitivity to NE produced by varying the concentrations of Mg++ were comparatively less. In the presence of EDTA, vas deferens obtained from reserpinized animals showed subsensitivity in normal and Mg++ excess media and supersensitivity in Mg++ free medium. In the presence of EDTA, reserpinized preparations showed slight supersensitivity in normal Mg++ medium, marked supersensitivity in Mg++ free and lesser subsensitivity in Mg++ excess medium. Probably EDTA by more effectively removing Mg++ from the membrane binding sites by chelation makes the membrane permeable to Ca++ leading to supersensitivity to NE (observed only in the presence of EDTA). These results suggest that the failure of reserpine to induce supersensitivity to NE in rat vas deferens may be due to an enhanced antagonism of Mg++ on Ca++ movements in this preparations due to the poor capacity of rat tissue to retain Ca++.

Norepinephrine: stimulated activity of hypothalamic adenylate cyclase varies throughout the estrous cycle of the female rat

The activity of hypothalamic adenylate cyclase was studied throughout the estrous cycle of the female rat. The activity of the enzyme was determined in particulate fractions obtained from hypothalami of rats killed at 10.00 h and 16.00 h of the 4-day estrous cycle. The activity was assayed in the presence of norepinephrine (10(-8) to 10(-3) M) by the capacity to produce adenosine 3',5' cyclic monophosphate. The basal activity of adenylate cyclase was higher in the morning of estrus than at any other time during the cycle. Norepinephrine-stimulated adenylate cyclase activity, as assessed by the apparent affinity (Kd) and apparent maximum effect, varied during the cycle, showing highest affinity, lowest Kd, in the afternoon of proestrus. The highest level of apparent maximum effect was also found in the afternoon of proestrus declining on diestrous day 2, diestrous day 1 and estrus. The norepinephrine stimulated activity was significantly inhibited by phenoxybenzamine, an alpha-blocker, in the morning of diestrus day 1, whereas on the day of diestrus day 2 and proestrus it was inhibited by the beta-adrenoblocker, propranolol. A similar degree of inhibition by alpha- and beta-blockers was observed in the morning of estrus. These results indicate that the hypothalamic adenylate cyclase coupled to adrenergic receptors shows dynamic changes throughout the estrous cycle

The antiadrenergic effects of hypermagnesemia: an experimental study

The circulatory effects of norepinephrine (4 * g/kg) and phenylephrine (20 */kg) were determined in anesthetized dogs withnormal plasma magnesium and with induced hypermagnesemia. Norepinephrine caused a 24% increased in heart rate by 103% increase in the systemic vascular, resistance index in normomagnesemic dogs, while with hypermagnesemia the variations were of 13% and 1%, respectively. Isoproterenol increased heart rate by 485 and 185 in dogs with normo- and hypermagnesemia, respectively.Phenylephrine increased the systemic vascular resistance index (74%) only in the normomagnesemic state.The effects of all the drugs were significantly defferent (P<0.01), without and with the simultaneous administration of magnesium sulfate (plasma magnesium, 1.3ñ0.2mEq/l and 6.8ñ1.1 mEq/l, respectively).We conclude that acute induced hypermagnesemia antagonizes the circulatory effects of adrenergic stimulation, a fact that may explain its antiarrhythmic and hemodynamic effects during acute myocardial ischemia

Influência dos adrenoceptores alfa1 e alfa2 do hipotálamo médio sobre a pressao arterial sistêmica em ratos / Role of the alfa1 and alfa2 adrenoceptores in the medial hypothalamus on the arterial pressure in rats

Foram estudados os efeitos sobre a pressäo arterial sistêmica após a administraçäo de noradrenalina e de dois antagonistas de alfa-adrenoceptores no hipotálamo médio de ratos normotensos. Tanto o prazosin quanto a ioimbina antagonizaram a açäo do agonista misto de alfa1/alfa2-adrenoceptores, a noradrenalina ; entretanto a administraçäo prévia de prazosin mostrou uma maior interaçäo da noradrenalina pelos adrenoceptores alfa1. Estes resultados sugerem que os adrenoceptores alfa1 do hipotálamo médio exerceriam uma maior influência que os adrenoceptores alfa2 no controle de pressäo arterial sistêmica

Spasmolytic activity of two synthetic anilide local anaesthetics.

Two basic anilides EA-7 and EA-8 were investigated for their antispasmodic activity against a variety of spasmogens on different tissues from different species of animals and comparison was made with lignocaine. EA-8 was found to be the most potent in this respect, followed by EA-7 and lignocaine. The antispasmodic potency does not correspond to their local anaesthetic potency. This suggests a direct depressant effect on tissues.