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One of the side actions which restrict the clinical use of reserpine is a strong and long-lasting mental depression. Looking for other reserpine-like alkaloids less toxic and more useful for clinical trials than reserpine, Velluz et al. (1, 2) have presented 10-methoxydeserpidine (decaserpine), an isomer of reserpine. The pharmacological effects of decaserpine have been reported in detail by Mir and Lewis (3). When the initial blood pressure of an anesthetized cat was considerably high, the intravenous injection of decaserpine caused a gradual fall and bradycardia , and increased the pressor responses to adrenaline and noradrenaline. The intraperito neal injection of 20 mg/kg of decaserpine did cause neither ptosis , diarrhea nor sedation in rats. In mice, however, the intraperitoneal injection of 40 to 80 mg/kg of decaserpine induced drowsiness and decrease of spontaneous motor activity in a similar manner to the appropriate dose of reserpine. On the other hand, Leroy and Schaepdryver (4) have reported that the intra

The depressant effect of reserpine on the spontaneous contraction and transmem brane potentials of the isolated atrial preparation of rabbit has been described in detail in the previous reports (1-4). A rise instead of fall in the blood pressure due to reserpine, the reserpine reversal, was demonstrated in the dog and cat pretreated with monoamine oxidase inhibitors (5, 6). Shore and Brodie (7) found that administration of reserpine to rabbits pretreated with iproniazid resulted in the sympathetic excite ment. However, Eltherington and Horita (6) observed no sign of the reserpine reversal after amphetamine in mice. Shimamoto and Torii (8) observed that pretreatment of rabbits with iproniazid reversed the response of the blood pressure and the behavior to the intravenous injection of reserpine.Toda (9) of this laboratory observed that the application of monoamine oxidase inhibitors to the isolated rabbit atrium did not reverse, but delayed onset of the effect of reserpine on the atrial transmembrane potential.Recently, Goldberg and Shideman (10) have shown that the intraperitoneal injection of a monoamine oxidase inhibitor, SKF-385, depletes the myocardial noradrenaline in cats, and conversely, accumulates it in rats. Matsuo (11) . of this laboratory has shown that the application of SKF-385 to the isolated atrium of rabbit does not produce sig nificant changes in the noradrenaline content of the atria. Pepeu et al. (12) demonstrated that the pretreatment of the guinea-pig atrium with iproniazid prevented the spon taneous depletion of noradrenaline from this tissue, but that with PIH did not so.To elucidate the mechanism of the reserpine reversal on the spontaneous contraction of the isolated atrial preparation of rabbits, the effects of the monoamine oxidase inhibitors on the depressant action of reserpine were studied. METHODSAlbino rabbits, 2.0 to 2.5 kg of body weight, were used. Animals were killed by cutting both common carotid arteries. Immediately thereafter the heart was extirpated, and the atrium was separated from the ventricle.The atrial preparation was

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The increase in myocardial contractile force after administration of epinephrine is closely related to the activation of cyclic 3', 5'-AMP with a subsequent conversion of phosphorylase b to a (1-5). Further, it seems likely that there exists a close relationship between the level of circulating catecholamine and the activity of phosphorylase in the heart, based on the finding that the injection of ganglionic stimulating agents produces the simultaneous increase in myocardial contractile force and augmentation of phos phorylase activity (6). The observation of Nakatani (7) that physostigmine augments phosphorylase activity in the heart and this augmentation is prevented by prior reser pine is compatible with the view that endogenously liberated catecholamines increase phosphorylase a. However, there are controversial reports regarding the effect of reserpine on heart