双苄基异喹啉类生物碱的心血管药理作用

Tetrandrine, dauricine, daurisoline and neferine are bisbenzylisoquinoline alkaloid derivatives isolated from Chinese traditional medicine and herbs. The cardiovascular pharmacological effects and the mechanism of actions of these compounds were reviewed. Tetrandrine isolated from Stephania tetrandra S Moore possesses antihyper-tensive and antiarrhythmic effects. The antihypertensive effects of tetrandrine have been demonstrated in experi-mental hypertensive animals and in hypertensive patients. Recent studies showed that in addition to its calcium antagonistic effect, tetrandrine interacted with M receptors. Modulation by M receptor is one of the pharmacologi-cal mechanisms of cardiovascular effects of tetrandrine. Dauricine and daurisoloine were isolated from Menispermum dauricum DC. The antiarrhythmic effects of dauricine have been verified in different experimental arrhythmic models and in cardiac arrhythmic patients. Dauricine blocked the cardiac transmembrane Na ,K and Ca2 ion currents. Differin     

Pharmacology, clinical efficacy and adverse effects of vindesine sulfate, a new vinca alkaloid

Vindesine is a new vinca alkaloid antineoplastic agent derived from vinblastine. However, its antineoplastic spectrum more closely resembles that of vincristine. Clinical studies indicate activity against acute leukemia, lung cancer, carcinoma of the breast, squamous cell carcinoma of the esophagus and head and neck, Hodgkin's disease and non-Hodgkin's lymphomas. Pharmacokinetic studies indicate that vindesine exhibits a triphasic elimination pattern with a terminal half-life of 24.2 hours. Elimination is primarily through hepatic metabolism. The major side effects associated with vindesine therapy are myelosuppression and neurotoxicity. Other side effects include alopecia, nausea and vomiting and local tissue irritation associated with extravasation. Vindesine will be a positive addition to the antineoplastic armamentarium. The full extent of its activity remains to be established.     

Cardiovascular effects of a new dihydropyridine calcium antagonist

The effects of methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo- 1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate (DHP-218), a 1,4-dihydropyridine derivative, on the cardiovascular system and myocardial oxygen consumption were investigated. Effects on cardiovascular system: In urethane-alpha-chloralose anesthetized dogs, DHP-218 at a dose of 0.01 mg/kg i.v. decreased blood pressure (BP), and at 0.03 mg/kg i.v., long-lasting BP decrease was accompanied by an increase in heart rate (HR), and an increase in blood flow of the coronary, vertebral and internal carotid arteries. No significant changes in myocardial contractile force (MCF) and blood flow of the common carotid and renal arteries were observed. The duration of action was different for various effects. At doses more than 0.05 mg/kg i.d., blood pressure decreased and HR, MCF and the blood flow of coronary and vertebral arteries increased. The effects of nifedipine on the cardiac and regional blood flow were observed at doses more than 0.001 mg/kg i.v. and 1 mg/kg i.d., but the duration of its action was very short compared to those of DHP-218. Effects on cardiohemodynamics: In urethane-alpha-chloralose anesthetized dogs, DHP-218 at a dose of 0.01 mg/kg i.v. produced a decrease in BP and total peripheral resistance (TPR) and an increase in cardiac output (CO). At a dose of 0.03 mg/kg, a decrease in BP and TPR and increases in HR and CO were observed. The duration of action was different for various parameters. No significant changes in dp/dtmax, stroke volume and cardiac work were observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular effects of KM-13, a new, orally effective, cardiotonic sympathomimetic amine

Dobutamine's chemical structure was modified to make it orally effective, while its pharmacological profile was preserved. Testing on anesthetized dogs showed that replacement of the para hydroxyl group with carboxyamide at the phenyl end of the molecule increased inotropic potency threefold, but it introduced pressor activity that spoiled the inotropic selective profile of dobutamine. However, shifting carboxyamide to the meta position avoided pressor activity and further enhanced inotropic potency to nine times that of dobutamine. When administered orally to conscious dogs, this compound, KM-13 (5 mg/kg), produced a sustained increase in left ventricular dP/dt with only immediate changes in heart rate; 10 mg/kg dobutamine was without cardiovascular effects. The (-) isomer of KM-13 contained twice the inotropic activity of the (+) isomer; in contrast, the (-) isomer had no effect on diastolic blood pressure, while the (+) isomer lowered blood pressure. The inotropic and chronotropic effects of dobutamine and KM-13 are both largely due to beta-adrenergic stimulation as shown by propranolol blockade. In contrast to dobutamine, KM-13 is an agent that is active by either oral or buccal administration and has greater inotropic potency.     

Xylopyrine-F, a new cyclopeptide alkaloid from Zizyphus xylopyra

A new 14-membered ring cyclopeptide alkaloid xylopyrine-F, together with known alkaloids nummularine-P and sativanine-H, has been isolated from the root bark of Zizyphus xylopyra and their structures were established by chemical and spectral evidences.     

Xylopyrine-F, a new cyclopeptide alkaloid from Zizyphus xylopyra

A new 14-membered ring cyclopeptide alkaloid xylopyrine-F, together with known alkaloids nummularine-P and sativanine-H, has been isolated from the root bark of Zizyphus xylopyra and their structures were established by chemical and spectral evidences.     

Cycleanine N-oxide, a new alkaloid from Synclisia scabrida

A phytochemical investigation of the stems of SYNCLISIA SCABRIDA M IERS (Menispermaceae) resulted in the isolation of a number of known bisbenzylisoquinoline alkaloids: cycleanine, norcycleanine, cocsuline and cocsoline. A new alkaloid, cycleanine N-oxide was also isolated.     

Xylopyrine-C, a new cyclopeptide alkaloid from Zizyphus xylopyra

Xylopyrine-C, a new 14-membered ring cyclopeptide alkaloid, has been isolated from the root bark of Zizyphus xylopyra together with a known alkaloid scutianine-C, and their structures were established by chemical and spectral evidences.     

Xylopyrine-C,a new cyclopeptide alkaloid from Zizyphus xylopyra

Xylopyrine-C, a new 14-membered ring cyclopeptide alkaloid, has been isolated from the root bark of Zizyphus xylopyra together with a known alkaloid scutianine-C, and their structures were established by chemical and spectral evidences.     

Bowdichine, a new diaza-adamantane alkaloid from Bowdichia virgilioides

A novel alkaloid named bowdichine (1), only the third with a diaza-adamantane skeleton containing an unusual N-acetyl enamine moiety, and the known alkaloids acosmine (2), ormosanine (3) and podopetaline (4) have been isolated from the stem bark of Bowdichia virgilioides. The structures were elucidated on the basis of spectral data, mainly 1D and 2D NMR of the diaza-adamantane alkaloids 1 and 2.     

Xylopyrine-C, a new cyclopeptide alkaloid from Zizyphus xylopyra

Xylopyrine-C, a new 14-membered ring cyclopeptide alkaloid, has been isolated from the root bark of Zizyphus xylopyra together with a known alkaloid scutianine-C, and their structures were established by chemical and spectral evidences.     

Angelicastigmin, a new eserine alkaloid from Angelica polymorpha

Angelicastigmine (1), which belongs to the relatively seldom group of eserine alkaloids, was isolated as new alkaloid from the roots of Angelica polymorpha Maxim. The structure was elucidated by spectroscopic methods.     

Cardiovascular effects of irindalone, a new S2-serotonergic antagonist, in the rat

Irindalone is a new antihypertensive agent with affinity to serotonin (5-HT2) receptors and at higher concentrations also to alpha 1-adrenoceptors. The present study was designed to evaluate the relative importance of the antagonism of central and peripheral alpha 1- and 5-HT2-receptors in the blood pressure lowering properties or irindalone after acute administration. In conscious Sprague-Dawley rats intravenous irindalone (0.05-1.5 mg/kg) dose-dependently reduced the blood pressure. In the same dose-range irindalone antagonized pressor responses to phenylephrine and electrical stimulation of the spinal sympathetic outflow (SNS) in the pithed rats, indicating that the acute blood pressure lowering effect is primarily related to the blockade of alpha 1-adrenoceptors. However, the concomitant 5-HT2-receptor blockade may contribute since irindalone in a dose (0.15 mg/kg) where it had no alpha-adrenoceptor blocking properties enhanced the hypotensive response to selective alpha 1-adrenoceptor blockade by prazosin (1 micrograms/kg). We found no evidence that central mechanisms contributed to the blood pressure lowering effect of irindalone. In anaesthetized rats irindalone (1 mg/kg) did not reduce the directly recorded sympathetic nerve activity. Intracerebroventricular administration of irindalone in conscious rats (10-100 micrograms) had no consistent effects on the blood pressure and did not enhance the hypotensive response to intracerebroventricularly administered prazosin (10 micrograms). Finally, the hypotensive response to irindalone was not influenced by depletion of central serotonin stores (by PCPA). It is concluded that the blood pressure lowering effect of irindalone following acute administration is related primarily to blockade of peripheral alpha-adrenoceptors but that the concomitant blockade of 5-HT2-receptors may contribute.     

Cardiovascular and renal effects of acute administration of a new hypotensive compound,guancydine

Summary Oral administration of a single 500 mg dose of guancydine rapidly (30 mins) produces a marked fall in systolic and diastolic blood pressure, which lasts for at least 6 h, and is accompanied by tachycardia. Hypotension and tachycardia are more marked on standing, but conspicuous postural falls seldom occur. The decrease in blood pressure does not depend on angiotensin antagonism by guancydine, as pressor responses to angiotensin, as well as to noradrenaline, are not diminished by the drug. Marked fluid and electrolyte retention also occurs after guancydine administration, and is probably due to a reduction in glomerular filtration rate and increased tubular reabsorption of sodium. The time course of the various effects of guancydine closely parallels changes in the plasma concentration of the drug. A very precise quantitative relationship exists between the hypotensive effect and the log of plasma guancydine concentrations between 1 and 5 µg/ml.     

Cardiovascular responses elicited by intrathecal kinins in the conscious rat.

In the conscious, unrestrained rat, intrathecal (i.t.) injection of 0.81 pmol-81 nmol bradykinin (BK), kallidin (KD) and T-kinin at the T-9 spinal cord level produced transient (less than 10 min) increases in mean arterial pressure (MAP) and longer lasting decreases in heart rate (HR). These effects were dose-dependent and similar with respect to intensity and time course for the three kinins. The des-Arg9-BK fragment, a selective agonist for B1 receptors, was active only at 81 nmol. The pressor response induced by BK was enhanced by propranolol and by transection of the cervical spinal cord but was converted to a vasodepressor effect by prazosin. The bradycardia was converted to tachycardia by prazosin, atropine, pentolinium, capsaicin and in spinal transected rats. However, the cardiovascular responses to BK remained unaffected by diphenhydramine plus cimetidine, morphine, indomethacin, adrenal medullectomy, i.t. idazoxan and after bulbospinal noradrenaline deafferentation with 6-hydroxydopamine. These results suggest that the increase in MAP induced by i.t. BK is mediated by the sympathoadrenal system while the decrease in HR is ascribable to a vagal reflex involving sensory C-fibers and a spinobulbar pathway. This pharmacological evidence therefore supports a role for kinins in cardiovascular regulation in the spinal cord.     

Oripavine - a new opium alkaloid

Oripavine was isolated from the dried capsules of a variety of PAPAVER SOMNIFERUM cultivated on Tasmania.