PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Papaverine”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1978

Metabolism of papaverine IV. Urinary elimination of papaverine metabolites in man.

1. A gas chromatographic method is described for the quantitative determination of the metabolites of papaverine in urine. 2. The urinary excretion of papaverine metabolites was studied in man. About 50% of the metabolites of papaverine are excreted in the urine within 48 h. 6-Desmethylpapaverine is the major metabolite in the urine. The metabolites are excreted almost completely in conjugated form.

Biotransformation↗
PubMed1977

The inhibitory effect of papaverine on respiration-dependent contracture of guinea pig taenia coli in high-K medium. III. The differential effect of papaverine and rotenone on DT diaphorase.

The differential effects of papaverine (Pap) and rotenone (Rot) were studied on the highly respiration-dependent contracture of guinea pig taenia coli in 40 mM potassium (40-K) medium, on isolated DT diaphorase activity and on mitochondrial respiration. The inhibition of guinea pig taenia coli to the 40-K induced tension by Rot (5 x 10(-7)M) was fully reversed by the addition of a water soluble vitamin K3 (VK3) derivative or menadione sodium bisulfite (MSB). A low concentration (10(-7)--10(-6)M) of Pap which had no effect on the 40-K induced tension inhibited the VK3 restored tension from the Rot suppression, corresponding to a Pap inhibition of the isolated DT diaphorase. Inhibition of the effective concentration of Pap to the 40-K induced tension development was never reversed by addition of VK3 or MSB. In taenia coli, both MSB and VK3 established a bypass of the Rot sensitive site on the mitochondrial respiratory chain by means of the DT diaphorase system. The difference in washout-efficacy between Pap and Rot on the inhibition of 40-K induced tension was ascribed to a difference in their mitochondrial binding properties.

Animals↗
PubMed1977

Effect of papaverine on the frequency-force relationship in guinea-pig left atria.

Contractile responses of guinea-pig atria to papaverine were analyzed under different stimulation frequencies. Atria, driven at 2 Hz, showed positive inotropic responses to papaverine which were maximal within 10-15 min. These responses were maintained for 60 min in the presence of low concentrations of papaverine (up to 10(-5) M), but reversed into marked negative inotropic effects under the influence of higher concentrations. The well-known frequency-force relationship was reversed by papaverine. At low stimulation rates papaverine elicited positive inotropic responses, which gradually decreased with increasing frequencies until strong cardiodepression occurred. A frequency-force curve obtained in the presence of both the Ca2+-antagonistic drug D 600 and the inhibitor of the phosphodiesterase theophylline was similar to that obtained under the influence of papaverine. Theophylline alone evoked positive inotropic effects at all frequencies studied and left the character of the ascending staircase unchanged. In contrast, D 600 was ineffective at low, but cardiodepressive at high stimulation frequencies. In the presence of D 600 or papaverine high external Ca2+ could not restore a normal frequency-force relationship. The reversal of the frequency-force relationship as produced by D 600 and papaverine could not be obtained by lowering of the external Ca2+. The present results show that papaverine is able to evoke marked positive inotropic effects at low stimulation frequencies by inhibition of phosphodiesterase. At high frequencies, however, these effects are masked by negative inotropic responses due to the inhibitory action of papaverine on Ca2+-exchange of the cardiac muscle cell.

Animals↗
PubMed1975

Effects of papaverine on isolated rabbit papillary muscle.

The effect of papaverine on the positive inotropic response to isopreqaline and to calcium was studied on the rabbit isolated papillary muscle; theophylline and the calcium antagonistic D600 were used for comparison. The dose-response curve for isoprenaline was shifted to the left by papaverine (3 times 10- minus 6 to 3 times 10- minus 5 M), in a dose-dependent manner, while that for calcium was not affected by the same concentration. In this respect papaverine was about 30 times more potent than theophylline. In the presence of papaverine isoprenaline induced arrhythmic contractions of the papillary muscle: the incidence of arrhythmic contractions was positively correlated to the concentration of papaverine. Papaverine 10- minus 5 to 10- minus 4 M caused only a positive inotropic response whereas 3 times 10- minus 4 to 10- minus 3 M induced a biphasic response, i.e., after a positive inotropic effect followed a negative one. In the presence of 3 times 10- minus 4 M papaverine isoprenaline failed to cause a positive inotropic response but exclusively induced arrhythmic contractions. Calcium, on the other hand, readily antagonized the negative inotropic effect of papaverine (3 times 10- minus 4 M) and caused a contracture of the papillary muscle. The results indicate that papaverine (3 times 10- minus 6 to 10- minus 5 M) like theophylline (10- minus 4 to 10- minus 3 M) produces its effect by phosphodiesterase inhibition and thereby specifically potentiates the response through beta-adrenoceptor stimulation. In higher concentrations (3 times 10- minus 4 to 10- minus 3 M) it acts as a calcium antagonistic, like D600, and furthermore may interact with calcium moving through myocardial cell membranes to cause a contracture via a mechanism which it shares with theophylline.

Animals↗
PubMed1978

[Effect of papaverine on the tonus and contraction of depolarized taenia coli musculature in guinea pigs].

Experiments were performed on the isolated strips of guinea pig taenia coli. The smooth muscle was depolarized in a solution with high potassium concentration (120 mM KCl). The effect of papaverine (in concentration of from 10(-5) to 3.10(-5) g/ml) on the tonus and the contractile off-response originating after the ending of longlasting strong polarizing current was investigated. It was found that: 1) papaverine abolished the concentrations induced by drugs (histamine, acetylcholine, bradykinin); 2) papaverine reduced the tonus of depolarized muscle and eliminated its increase under the effect of a rise of the external calcium concentration; 3) papaverine had no effect on the amplitude and the ascending phase of the contractile off-response; 4) papaverine accelerated the discending phase of the contractile off-response. The data obtained suggest: 1) there are chemoexcitable calcium channels in the cellular membrane which are blocked by papaverin; 2) there are calcium "leakage" channels in the cellular membrane responsible for the tone maintenance which are blocked by papaverine; 3) papaverine has a negligible effect on the electroexcitable calcium channels.

Animals↗
PubMed1975

Papaverine: its effects on cyclic AMP in vitro and psoriasis in vivo.

Psoriatic epidermis shows excessive cell proliferation, incomplete morphogenesis, and glycogen accumulation. These three features may result from coordinate misregulation by the previously reported abnormal lesional ratio of cyclic AMP/cyclic GMP. If so, it is possible that psoriasis might improve by topical application of an agent known to alter cellular levels of cyclic nucleotides. In the present study papaverine (3.0 x 10-4 m) produced a 210percent increase (.02 smaller than p smaller than .05) in epidermal cyclic AMP levels in vitro. Therefore, 1 percent papaverine cream (approximately 2.7 x 10-2m papaverine) was chosen to establish whether a cyclic AMP elevating agent could improve a soriatic lesion. A double-blind comparison of 1 percent papaverine cream versus cream alone was conducted on matched lesions in 45 patients. Of those patients showing differential improvement (i.e., only one lesion of the pair improved), 81 percent (p=0.011) of those showing a response in the center of the lesion and 77 percent (p=0.046) of those improving at the edge had applied papaverine. Although no attempts were made to develop a papaverine formulation with immediate therapeutic utility, the numerically significant papaverine results suggest future therapeutic developments.

Animals↗
PubMed1979

Comparative study of the clinical effect of vincamine versus papaverine given parenterally in the acute phase of stroke.

The efficacy of the "oxygenator", vincamine was assessed in comparison to a classic vasodilator, papaverine, after parenteral administration during the first days of an acute thrombo-embolic stroke. All 263 patients admitted to this open trial had a thrombo-embolism of the A. carotis or one of its cerebral branches within the previous 24 h. Patients demonstrating minimal neurological deficit or requiring admission to an intensive care unit, or patients with a suspected hemorrhagic syndrome were excluded. Each patient received i.v. infusions (15 mg X 6) of 6 vials of vincamine per 24 h, or 6 vials of papaverine (40 mg X 6) per 24 h, occasionally in combination with acetylsalicylic acid (ASA), dipyridamol and hydrocortisone. An initial 3-h control was followed by regular surveillance for 5 days, paying special regard to consciousness and motricity. The administration of vincamine alone had a significantly more favourable effect than papaverine alone on consciousness (p less than 0.001). Furthermore, vincamine associated with other drugs was significantly superior (p less than 0.01) to papaverine given in association. A similar tendency was noted for motor recuperation after vincamine compared to papaverine (p less than 0.001). Vincamine and papaverine were well tolerated during the 5-days observation period, only one side effect after vincamine and four after papaverine being noted.

Adult↗
PubMed1976

A comparative study between the cardiovascular effects of cetiedil, a new vasodilator, and papaverine and aminophylline.

The cardiovascular effects of progressively increasing infusions of papaverine hydrochloride, aminophylline and cetiedil, a new vasodilator, were studied and compared in the anesthetized intact dog preparations. Papaverine and aminophylline had qualitatively the same effects on the various parameters, but in general the maximal effects of papaverine were of a greater order of magnitude. Cetiedil exhibited a different pattern of cardiovascular activity characterized by initial decrease in mean pulmonary arterial flow of 16% accompanied by an increase in systemic vascular resistance of 28% and in pulmonary vascular resistance of 19%, a stage of restoration of mean pulmonary arterial flow to control level accompanied by decrease in dp/dt of 25% and increase in pulmonary vascular resistance of 27% and a final stage of decrease in mean pulmonary arterial flow, representing toxic effects and accompanied by decrease in mean aortic pressure of 26%, dp/dt of 54% and heart rate of 27%, and an increase in pulmonary vascular resistance of 84%. These results indicate that cetiedil is devoid of cardiac stimulant activity. In another group of experiments devoted to measurement of vascular resistance of the hind limb, the results indicate that cetiedil, like papaverine and aminophylline, increased femoral blood flow through a decrease in resistance of the hind limb vasculature. This increase in flow could have been brought about only by redistribution of the cardiac output through differential effects on different vascular beds, since unlike papaverine and aminophylline, cetiedil does not increase cardiac output. The lesser maximal increase in femoral blood flow following cetiedil as compared to that following papaverine is probably referable to the relatively limited capacity of redistribution of the cardiac output to augment femoral blood flow. Superimposition of cetiedil and aminophylline on maximal effects of papaverine led to an additional decrease in mean femoral perfusion pressure, probably implying differences in basic mechanisms by which the three agents bring about their smooth muscle relaxant action.

Aminophylline↗
PubMed1975

The absence of stimulation of lipolysis by papaverine, a strong inhibitor of phosphodiesterase.

Quantitative studies of the action of theophylline and papaverine were performed in rat epididymal fat pads, both on the lipolytic effect and on the activity of phosphodiesterase, adenylate cyclase and protein kinase. Papaverine, a stronger inhibitor of phosphodiesterase than theophylline, did not produce lipolysis. The maximum lipolytic effect (glycerol release) of theophylline was much higher than that of epinephrine and nearly approached the effect exerted by dibutyryl cyclic AMP. While theophylline potentiated or was without any effect on lipolysis produced by epinephrine and dibutyryl cyclic AMP, papaverine at concentration 10- minus 3 M reduced the effect of both drugs as well as of theophylline by 90 per cent. These concentrations of papaverine also strongly inhibited the activity of adenylate cyclase. Neither papaverine nor theophylline prevented the activation of protein kinase by cyclic AMP. The data suggest that the lack of a lipolytic effect of papaverine migth be caused by a combination of its inhibitory effect on adenylate cyclase and direct inhibition of activation of triglyceride lipase.

Adenylyl Cyclases↗
PubMed1979

[Comparative studies on the chemical modifications of Ehrlich ascites tumor cell membranes by hydrophobic drugs (cepharanthine, papaverine and cholesterol) (author's transl)].

Comparative studies were done on the actions of hydrophobic drugs (cepharanthine, papaverine and cholesterol) regarding chemical modifications of Ehrlich ascites tumor cell membranes. Changes in membrane potential monitored by using cyanine dye (diS-C3-(5)) were induced by cepharanthine and papaverine, but not by cholesterol. Increase in membrane permeability of K+ ions induced with lysolecithin was strongly inhibited in the order of papaverine, cholesterol and cepharanthine. Oxygen uptake by the cells was also strongly inhibited by papaverine, but the inhibitory effect by cepharanthine was little and cholesterol had no effect. Membrane fluidity was decreased in the order of cholesterol, cepharanthine and papaverine. From these results, it was suggested that papaverine maintained the compartmentation of K+ ion and membrane fluidity by regulating the intracellular mitochondrial metabolism or by inhibiting the membrane bound ATPase nucleotidase activity. The membrane stabilizing effect of cepharanthine and cholesterol probably was due to decrease in the membrane fluidity because of the hydrophobic association to the lipid bilayer of the cell membranes.

Alkaloids↗
PubMed1975

Actions of various methylxanthines and papaverine on the synthesis of corticosterone in vitro.

Actions of various methylxanthines (theophylline, theobromine, caffeine) and papaverine, i.e. drugs which are known to inhibit phosphodiesterase (PDE), were studied on the basal and stimulated synthesis of corticosterone in vitro by using rat adrenal slices. When slices were incubated with methylxanthines, the synthesis of corticosterone was slightly increased. The order of potency, expressed as the efficacy (intrinsic activity) was: theophylline greater than caffeine greather than theobromine. Papaverine did not stimulate the synthesis. The synthesis stimulated by ACTH or the dibutyryl derivative of c-AMP (DBA) was reduced by all of the inhibitors of phosphodiesterase. The molar concentration of the inhibitors which reduced the stimulated steroidogenesis by 50% was lowest for papaverine, higher for theobromine and theophylline and highest for caffeine. Papaverine was active in concentrations of about 10(-5)M, while the methylxanthines were effective in concentrations of 10(-3)--10(-2)M. When the PDE-inhibitors were added to the incubate simultaneously with the stimulant (ACTH or DBA), there was a delay of 60 min before the synthesis was completely blocked. When the stimulant was added 30 min before the administration of an inhibitor, the inhibitory action was no more evident. The inhibitory action of theophylline, but not that of papaverine, was reversed by washing adrenal slices free from the inhibitor, before adding the stimulant. The type of inhibition for papaverine as well as for methylxanthines in antagonizing both the ACTH- and DBA-stimulated synthesis of corticosterone was not competitive but of a mixed type.

Adrenal Glands↗
PubMed1977

Effects of D 600 and papaverine on the inotropic response to isoprenaline on left guinea-pig atria under the graded influence of changes of frequency and temperature.

Isolated left guinea-pig atria were used to examine the influence of D 600 and papaverine on baseline contractile function and inotropic response to isoprenaline, under variable conditions of temperature (27 degrees to 42 degrees C) and rate of beat (0.125 to 4 Hz). The inotropic stimuli, caused by increasing the frequency of stimulation and decreasing the temperature, could not overcome the depressive action of D 600 on basal systolic tension. In addition the inotropic effects evoked by papaverine at low rates of beat and high temperatures were converted into cardiodepressive effects at high stimulation rates and low temperatures. The inotropic response to isoprenaline appeared to be by far more resistant to the depressive actions of D 600 and papaverine than the baseline contractile function. Only at a stimulation frequency of 2 Hz, high concentrations of D 600 (3 X 10(-7)M) and papaverine(3 X 10(-5)M) reduced the response caused by isoprenaline. At a stimulation frequency of 0.5 Hz, however, D 600 left the inotropic responses to isoprenaline unchanged, whereas papaverine potentiated these responses. It appears from the present results that the frequency of stimulation and the temperature greatly modify the cardiodepressive actions evoked by D 600 and papaverine.

Animals↗
PubMed1975

Papaverine, cyclic AMP and the dependence of the rat aorta on extracellular calcium.

The spasmolytic effects of papaverine and dibutyryl cyclic AMP (db-cAMP) were compared on isometric contractile responses induced by addition of increasing amounts of external calcium to K+-depolarized or noradrenaline-stimulated rat aorta strips. Papaverine at a concentration active on depolarized strips (3 times 10(-5) moles/1) reduced the maximal contraction (Emax) elicited by Ca2+ in these preparations, while db-cAMP did not. Contrary to what was observed on depolarized aortae, the degree of inhibition of noradrenaline-stimulated strips did not decrease with increasing extracellular calcium concentration (Ca)e. Both db-cAMP and papaverine at a concentration which did not depress Emax (5 times 10(-6) moles/1) potentiated the relaxing effect of high (Ca)e on contractions elicited by noradrenaline. In conclusion, cyclic AMP is probably implicated in the mode of action of papaverine on the noradrenaline-stimulated rat aorta. At a concentration active on depolarized strips, papaverine is also able to impair contractility directly.

Animals↗
PubMed1978

Effect of papaverine on Ca2+ uptake by a mitochondrial fraction isolated from rat uterine smooth muscle.

A mitochondrial fraction was isolated from rat uterine smooth muscle. The effect of papaverine (3 X 10(-6), 10(-5), 3 X 10(-5), 10(-4) M) on Ca2+ accumulation by the fraction was studied. The effect of papaverine was changed by using different substrates for Ca2+ accumulation. Papaverine inhibited the Ca2+ accumulation supported by glutamate plus ATP concentration-dependently. The Ca2+ accumulation supported by ATP alone was also inhibited. On the other hand, the Ca2+ accumulation supported by succinate and ATP was increased by papaverine. The effect was not concentration-dependent; papaverine (3 X 10(-5) M) was the most effective concentration for the effect with a shorter incubation (2 min).

Adenosine Triphosphate↗
PubMed1978

The role of cyclic AMP in temperature-dependent changes of contractile force and sensitivity ot isoprenaline and papaverine in guinea-pig atria.

Right and left guinea-pig atria responded to decreasing temperatures (42-27 degrees C) with elevation for force of contraction and concomitant increases in cAMP. When atria were rapidly cooled from 42 to 27 degrees C the increase in cAMP occurred prior to the onset of the inotropic responses. Papaverine (3 X 10(-5) M) potentiated the effects of temperature on cAMP and force of contraction on left atria driven at 0.5 Hz. On right atria beating spontaneously at frequencies above 2 Hz papaverine only potentiated the effect of decreasing temperatures on the response of cAMP but not on that of force of contraction. Time course studies of the effects of isoprenaline (3 X 10(-8) M) on right atria at 27 degrees C showed large inotropic responses to isoprenaline which were accompanied by increases in cAMP. At 42 degrees C the responses of force of contraction and cAMP to isoprenaline occurred faster and were only short-lasting. As with the time courses for isoprenaline, dose-response curves for the effect of isoprenaline and papaverine on cAMP content and force of contraction also appeared to be shifted towards higher levels at hypothemia. However, pD2 values reflected increases in affinity for inotropic, but not for the cAMP responses to isoprenaline and papaverine at hypothermia. These results show that cyclic AMP is involved in the inotropic responses to hypothermia, but not in the supersensitivity of heart to isoprenaline and papaverine as observed at low temperatures.

Animals↗
PubMed1979

A comparison of the inhibitory effect of cinnarizine and papaverine on the noradrenaline- and calcium-evoked contraction of isolated rabbit aorta and mesenteric arteries.

The inhibitory effects of cinnarizine and papaverine on the noradrenaline- and Ca-induced contraction of the rabbit thoracic aorta and mesenteric arteries have been compared. Papaverine was equally effective in reducing the contractile response evoked from both thoracic aorta and mesenteric arteries by the two modes of stimulation. Cinnarizine blocked the Ca-evoked contraction of the depolarized vessels but was less effective against the noradrenaline-induced contraction of the mesenteric arteries and even failed to antagonize the response of the thoracic aorta to noradrenaline. In Ca-free medium noradrenaline (10-5 M) evoked a fast non-sustained contraction. After readmission of CaCl2 a slow sustained contraction developed. In mesenteric arteries exposed to noradrenaline, cinnarizine selectively blocked the Ca0 dependent response while papaverine inhibited the initial fast response more than the Ca0 dependent one. These results suggest that cinnarizine and papaverine antagonize vascular contraction by different mechanisms. Cinnarizine seems to act by reducing membrane permeability to extracellular calcium. Papaverine inhibits the contraction by a main action on intracellular sequestration of activator calcium and to a lesser degree by an action similar to that of cinnarizine.

Animals↗