Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intracoronary injection of papaverine is used to determine coronary flow reserve in patients. The present study was to investigate the effect of papaverine on the performance of myocardium with reduced flow reserve. In nine anaesthetized open-chest dogs a bypass from the aorta to the left circumflex coronary artery (LCX) was established. Left ventricular end-diastolic and aortic pressure, dP/dt, stroke volume, LCX blood flow, and ECG were monitored. The performance of a segment of subendocardial wall supplied by the LCX was assessed by sonomicrometry. Peak reactive hyperaemia after 15s bypass occlusion was 1.44 +/- 0.09 times the baseline flow (41 ml/min), indicating reduced coronary flow reserve. Papaverine was injected into the bypass (0.3, 0.6, 1.2, 2.5, 5.0 mg/ml, 1 ml in 15s). The maximum LCX flow following PAPA 0.3 mg was comparable to peak reactive hyperaemia, but 10-15% higher after injection of 0.6-5.0 mg papaverine. Systolic shortening of the myocardium (control: 17.5% of end-diastolic length) became reduced in a dose-dependent fashion (5-25%) for about 1 min following papaverine injection. Stroke volume (control: 0.94 +/- 0.12 ml/kg) was reduced by about 8%, left ventricular end-diastolic pressure (control: 6.2 +/- 0.8 mmHg) increased by 15%, and dP/dtmin (control: 1850 +/- 150 mmHg/s) was curtailed by 15-25%. The ECG showed a transient T inversion and S-T depression following papaverine administration and in one experiment ventricular fibrillation occurred after the injection of 2.5 mg papaverine. The observed effects of intracoronary papaverine are consistent with the theory of transient subendocardial ischaemia arising from a redistribution of blood flow from the subendocardial to the subepicardial layers, because of greater vasodilatory capacity in the latter than in the former.
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PMID:Global and regional ventricular function following intracoronary application of papaverine. 177 71

Guinea-pig common bile duct preparations were used to quantify the spasmolytic potency of N-butylscopolamine (NBS), papaverine, gallopamil and nifedipine. A method was developed which allowed the measurement of intraluminal pressure changes in vitro. Barium chloride, carbachol and a solution with elevated potassium concentrations were used to stimulate smooth muscles. Concentration-response relationships for the spasmogens as well as for the spasmolytic drugs were evaluated in a cumulative manner. Furthermore, non-cumulative concentration-response curves were constructed for carbachol in the absence and presence of NBS. The -log EC50-values of the spasmogens were found to be 3.28 +/- 0.08 (BaCl2), 6.46 +/- 0.07 (carbachol) and 1.31 +/- 0.08 (KCl), respectively. The Emax values of carbachol and potassium were comparable, and were twice as high as the Emax of BaCl2. Papaverine was less potent than the calcium antagonists gallopamil and nifedipine, but proved capable of completely suppressing elevated muscular tone of the common bile duct preparation, independent of the stimulus used. NBS showed a high potency in suppressing only a carbachol-induced pressure increase, while it was rather ineffective when BaCl2 or a high potassium solution was used as the spasmogen. The concentration-response-curve for carbachol was shifted to the right in a parallel manner by NBS. Only a slight depression of Emax was observed. From the results it is concluded that NBS acts mainly as a muscarinic receptor antagonist. The high potency found for the calcium antagonists, gallopamil and nifedipine, in this model may indicate a possible role for these compounds in the treatment of biliary colic.
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PMID:Comparison of various spasmolytic drugs on guinea-pig isolated common bile duct. 177 88

1. To investigate whether cerebral vasodilatation by itself contributes to the decrease in ventilation as found during brain stem hypoxia the role of cerebral vasodilatation on minute ventilation was investigated in twelve cats anaesthetized with alpha-chloralose-urethane. 2. Cerebral vasodilatation in the medulla oblongata was produced by adding papaverine to the blood perfusing the brain stem. 3. Papaverine at concentrations of 10-35 micrograms per millilitre of blood had an appreciable depressant effect on ventilation. At a concentration of 14.3 micrograms ml-1 the depression in ventilation averaged 0.7 +/- 0.1 l min-1. 4. The ventilatory response to stepwise changes in papaverine concentration could be adequately described with a single exponential function with a time delay. 5. The time constant of the ventilatory response following a step increase in papaverine concentration (134 +/- 15 s) was longer than that of the step decrease (105 +/- 10 s) in concentration (P = 0.034). The time delays of the ventilatory response (88 +/- 21 s and 53 +/- 8 s respectively) were not significantly different (P = 0.126). 6. The ventilatory response to stimulation of the peripheral chemoreceptors by hypoxia and of the central chemoreceptors by hypercapnia was not impaired by papaverine. 7. The results support the hypothesis that cerebral vasodilatation by itself contributes to the decrease in ventilation by brain stem hypoxia.
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PMID:Effect on ventilation of papaverine administered to the brain stem of the anaesthetized cat. 182 33

We attempted to determine whether there is a possible link between the effect of papaverine on p-aminohippurate (PAH) accumulation, on cyclic nucleotide content and on certain other cellular functional parameters in rat kidney cortical slices in vitro. Papaverine at a concentration of 0.1 mM almost completely inhibited PAH accumulation in the slices. However, cyclic guanosine 3', 5'-monophosphate (cyclic GMP) and cyclic adenosine 3', 5'-monophosphate (cyclic AMP) levels in the slices were not significantly affected by papaverine at 0.1 mM, though papaverine at a concentration of 1 mM increased the cyclic GMP level without affecting the cyclic AMP level. Papaverine (0.1 mM) produced a decrease in the sodium gradient and in the adenosine triphosphate (ATP) level in the slices. Calcium uptake by mitochondria, isolated from kidney cortex, was apparently decreased in the presence of 0.1 mM papaverine. These results suggest that the inhibition of phosphodiesterase probably does not explain the action of papaverine on PAH accumulation in the slices. The inhibition of PAH accumulation by papaverine is partly a reflection of the fall in the sodium gradient in the slices treated with papaverine. In addition, a depression of ATP level in the slices and an inhibition of mitochondrial calcium uptake may be related to a possible mechanism of action of papaverine on PAH accumulation.
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PMID:Influence of papaverine on cyclic nucleotide level and cellular metabolism in rat kidney cortex in terms of its inhibitory effect on p-aminohippurate transport. 242 72

1. Dibutyryl cyclic AMP, injected towards the superior cervical ganglion of the cat, produced no consistent responses.2. Imidazole, injected towards the ganglion, regularly produced facilitation, both during intermittent and continuous preganglionic stimulation. This effect was dose-dependent and lasted 2-10 minutes.3. Aminophylline, injected towards the ganglion, regularly produced depression of ganglionic transmission, both during intermittent and continuous preganglionic stimulation. This effect was also dose-dependent and lasted 1-4 minutes. Papaverine produced the same type of response as aminophylline.4. Imidazole potentiated the ganglionic response to 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), while aminophylline depressed it.5. The results of the present experiments are consistent with the view that cyclic AMP may have a mediating role in the process of ganglionic transmission.
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PMID:The effect of N6-2'-O dibutyryl 3',5' cyclic adenosine monophosphate, imidazole and aminophylline on ganglionic transmission in the superior cervical ganglion of the cat. 436 81

The maximum upstroke velocity (Vmax) of Ca2+-dependent action potentials was used to measure relative changes in the slow inward current (Isi) caused by 10(-4) M papaverine as a function of pacing frequency in K-depolarized guinea pig ventricular strips. Papaverine caused a pronounced frequency-dependent depression of Vmax presumed to be correlated with a decrease in the rate of recovery from inactivation of Isi. Papaverine (10(-4) M) tripled the time constants for the biexponential recovery from depression of Vmax (determined by a paired pulse protocol) relative to the control. Depression of Vmax by papaverine during a 1 Hz stimulus train preceded by a long rest period reached a new steady state within three depolarizations. Complete poststimulation recovery from the depression of Vmax was also relatively rapid, unlike that described for verapamil. Preparations exposed to Mn2+ (after pretreatment with Ba2+ to restore excitability) showed a depressed steady-state Vmax independent of frequency. It is concluded that the frequency-dependent blockers of Vmax (papaverine and verapamil) differ in their rates of association and dissociation with the slow inward channel.
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PMID:Frequency-dependent depression of Vmax of slow response action potentials by a high concentration of papaverine. 618 48

1. The cardiovascular activity of S-(+)-boldine, an aporphine alkaloid structurally related to papaverine, was determined. The work includes functional studies on guinea-pig isolated aorta contracted with noradrenaline, caffeine, KCl or Ca2+, and on guinea-pig trachea contracted with acetylcholine or histamine. 2. S-(+)-boldine inhibited in a concentration-dependent manner the contractile response evoked by noradrenaline (10 microM) in guinea-pig aorta (IC50 = 1.4 +/- 0.2 microM) while the KCl depolarizing solution (60 mM)- or the Ca2+ (1 mM)-induced contractions were only partially affected by boldine up to 300 microM. In contrast, papaverine relaxed noradrenaline (NA), KCl or Ca2+ induced contractions showing similar IC50 values in all cases. S-(+)-boldine had a greater potency on the contraction elicited by NA whereas papaverine acted in a non-selective manner. 3. S-(+)-boldine was found to be an alpha 1-adrenoceptor blocking agent in guinea-pig aorta as revealed by its competitive antagonism of noradrenaline-induced vasoconstriction (pA2 = 5.64 +/- 0.08), and its potency was compared with that of prazosin (pA2 = 8.56 +/- 0.24), a known potent alpha 1-adrenoceptor antagonist. In contrast, papaverine caused rightward shifts of the NA concentration-response curves with depression of maximal response indicating that it acts as a non-competitive antagonist. 4. Contraction of guinea-pig aorta induced by caffeine (60 mM) in a Ca(2+)-containing Krebs solution was not affected by a 60 min incubation period with different doses of S-(+)-boldine (1-300 microM). Papaverine inhibited partially this caffeine-induced contraction at the maximal dose used (100 microM). 5. Inositol phosphates formation induced by noradrenaline (10 microM) in guinea-pig thoracic aorta was inhibited by S-(+)-boldine (30 microM) but not by papaverine (10 microM). 6. Contractions of guinea-pig trachea caused by acetylcholine (100 microM) or histamine (10 microM) were not modified by S-(+)-boldine (0.1-100 microM). 7. These results provide evidence that S-(+)-boldine, an aporphine alkaloid, has interesting properties as an alpha 1-adrenoceptor blocker in vascular smooth muscle, and acts as a competitive antagonist of the alpha 1-adrenoceptor present in the guinea pig aorta.
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PMID:The effect of S-(+)-boldine on the alpha 1-adrenoceptor of the guinea-pig aorta. 896 36

Long-term administration of morphine for the treatment of chronic pain produces constipation; this requires the use of laxatives, which impair water absorption and upset the electrolyte balance. Morphine-induced constipation is mainly due to inhibition of the propulsive movement of the gastrointestinal tract combined with spastic contraction of smooth circular muscles as a result of drug binding to opioid receptors in the tract. Since papaverine lacks affinity for opioid receptors but relaxes smooth muscle, it seemed possible that oral papaverine might be capable of diminishing constipation without impairing the analgesia achieved with morphine. For this purpose, experiments were carried out on rats: constipation was checked for by measuring the intestinal transit time, and analgesia was assessed by measuring the latency of the tail-flick response to radiant heat or nociceptive activity in single neurons of the thalamus evoked by supramaximal electrical stimulation of afferent C fibres in the sural nerve. Morphine and papaverine were administered by the oral route. Control animals received saline. To measure the intestinal transit time, India ink solution was given orally. Morphine (2.5 and 5 mg/kg orally) prolonged the transit time from approx. 420 min in the controls to more than 600 min, a dose of 2.5 mg/kg producing the maximum effect. Papaverine (0.5, 1, and 2 mg/kg) administered orally together with morphine significantly reduced morphine-induced constipation (Tables 1, 2). Papaverine given alone at a dose of 2 mg/kg caused no change in transit time, while 5 mg/kg significantly increased it (Table 2). The latency of the tail-flick response was increased by oral morphine (2.5 and 5 mg/kg) at 1, 2, and 3 h after administration. Papaverine (0.5, 1 and 2 mg/kg) given in combination with morphine left the antinociceptive effect of morphine unchanged (Figs. 1-3). A study of the nociceptive activity evoked in thalamus neurons of rats under urethane anaesthesia indicated that intestinal absorption of morphine was blocked. Therefore, metoclopramide (0.15 mg/kg) was injected i. v. 10 min before oral administration of morphine or the combination of morphine plus papaverine. Subsequently, morphine produced a dose-dependent depression of evoked nociceptive activity (Fig. 4), the mean effect amounting to 60 % of the control activity and being produced by 2.5 mg/kg (Fig. 5). Since in former experiments on nociceptive activity evoked in thalamus neurones it has been found that the ED(50) of i. v. morphine is 0.05 mg/kg, it is very likely that the presystemic elimination of orally administered morphine is very high and, in addition, that the efficiency of its active metabolite, morphine-6-glucuronide, is rather poor. When morphine 2.5 mg/kg was given together with papaverine 0.5 mg/kg, and morphine 5 mg/kg was administered in combination with papaverine 2 mg/kg, there was no significant reduction in the depressant effect of morphine on nociceptive activity evoked in thalamus neurons (Figs. 6, 7). The results suggest that papaverine given by the oral route may reduce morphine-induced constipation without impairment of the analgesic action of morphine in patients suffering from pain.
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PMID:[Oral papaverine prevents morphine-induced constipation without interfering with analgesia achieved with oral morphine]. 1279 74

The crude extract of aerial parts of St John's wort (Hypericum perforatum) (Hp.Cr) and its fractions were studied in vitro for its possible spasmolytic and bronchodilator activities to rationalize some of its medicinal uses. In rabbit jejunum preparations, Hp.Cr caused a concentration-dependent relaxation of both spontaneous and K+ (80 mm)-induced contractions at a similar concentration range (0.1-1.0 mg/mL), similar to that produced by papaverine, whereas verapamil was relatively potent against K+-induced contractions. Hp.Cr shifted the Ca2+ concentration-response curves (CRCs) to the right, similar to that caused by papaverine or verapamil and also caused leftward shift of isoprenaline-induced inhibitory CRCs, similar to papaverine. In guinea-pig tracheal preparations, Hp.Cr caused relaxation of carbachol and K+-induced contractions at similar concentrations (0.01-0.3 mg/mL) and also shifted the isoprenaline-induced inhibitory CRCs to the left, similar to that caused by papaverine. In rabbit aorta preparations at rest, Hp.Cr produced a moderate vasoconstriction, while exhibited vasodilator effect against phenylephrine and K+-induced contractions. Papaverine and verapamil also produced similar non-specific vasodilation, but were devoid of any vasoconstrictor effect. Hp.Cr caused suppression of atrial force of contractions at concentrations about 20 times higher than those that produced inhibitory effect in smooth muscle preparations, similar to papaverine. These results suggest that the spasmolytic effects of Hp.Cr are mediated through dual inhibition of calcium influx and phosphodiesterase (PDE)-like mechanisms, which might explain the medicinal use of St John's wort in the disorders of gastrointestinal and respiratory tracts. Furthermore, the presence of Ca2+ antagonist and PDE inhibitory-like constituents might also be contributing to some extent in the well established use of plant in depression.
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PMID:Antispasmodic and bronchodilator activities of St John's wort are putatively mediated through dual inhibition of calcium influx and phosphodiesterase. 1631 82

Papaverine has been associated with transient cranial nerve dysfunction after topical application during craniotomy. The authors report similar dysfunction after the use of papaverine affected brainstem structures. Two patients undergoing craniotomy for clipping of an aneurysm experienced bilateral depression of cortical somatosensory evoked potentials to both median and tibial nerve stimulation after administration of papaverine. Arterial blood gas analysis, hemodynamic parameters, and anesthetic levels remained constant throughout these somatosensory evoked potential changes. In addition, intraoperative angiography and immediate postoperative CT imaging showed intact blood flow with complete exclusion of the aneurysm. Both patients recovered within 1-2 hours and had normal neurological examination findings after extubation. Topical papaverine use may be associated with direct effects on brainstem structures. The transient nature of those changes suggests that aggressive intervention may not be needed. Maneuvers to limit the spread of papaverine to basal cisterns should be considered.
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PMID:Transient bilateral brainstem dysfunction caused by topical administration of papaverine. 2172 77


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