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Effect of intracarotid papaverine on human cerebral blood flow and vascular resistance during acute hemispheric arterial hypotension.

This study assessed the feasibility of augmenting cerebral blood flow (CBF) and decreasing hemispheric cerebrovascular resistance (CVR) by intracarotid papaverine during acute cerebral hypotension. Awake patients (n = 10) undergoing transfemoral balloon occlusion of an internal carotid artery (ICA) with nitroprusside (SNP)-induced systemic hypotension (10% reduction of mean arterial pressure) were studied. We measured mean femoral artery pressure (MAP), mean distal ICA pressure (P(ica)), and CBF (intracarotid 133Xe) at two time points: before and after intracarotid papaverine infusion (1 or 7 mg/min). Two patients became symptomatic immediately after ICA occlusion and were excluded. One patient developed a focal seizure during papaverine infusion. In another, the occlusion balloon deflated prematurely. Of the remaining six patients, two of the three patients who received high-dose papaverine (7 mg/min) developed transient obtundation. The remaining three patients, who received low-dose papaverine (1 mg/min), did not develop any neurologic symptoms. There was a trend for intracarotid papaverine to increase hemispheric CBF by 36% (33 +/- 10 versus 45 +/- 22 ml x 100 g(-1) x min(-1), P = .084, n = 6); papaverine decreased CVR from 1.3 +/- 0.4 to 1.0 +/- 0.3 mm Hg x ml(-1) x 100 g(-1) x min(-1) (P = .049). There was no significant change in heart rate, MAP, or P(ica) during experimental protocol. Manipulation of CVR by intracarotid papaverine during acute hemispheric arterial hypotension appears to be feasible. Further studies are needed to establish safety and efficacy.

Aged↗

Combined papaverine test and radionuclide penile blood flow in impotence: method and preliminary results.

The investigation of vascular impotence requires a simple, reliable and non-invasive method of estimating penile arterial supply. A method for measuring flow to the dependent portion of the penis has been developed using technetium-labelled red blood cells (99mTc-RBC). Its use, in conjunction with the intracavernous injection of papaverine, was investigated in 32 patients with various causes of impotence. Intracavernous papaverine was administered and a pneumatic cuff was inflated around the base of the penis both to isolate the penile circulation and to prevent dispersion of papaverine. The remaining blood pool was labelled with 99mTc-RBC. A gamma camera was used to produce a time-activity curve for the penis following release of the cuff. Penile blood flow was calculated from the initial gradient of the time-activity curve. Papaverine-stimulated penile blood flow was significantly greater in patients without evidence of arterial insufficiency. None of the subjects with arterial disease achieved flows greater than 20 ml/min/100 ml, while flow in patients without arterial disease exceeded this value. Flow estimation without the use of papaverine was not able reliably to discriminate between the 2 groups. There was no difference in papaverine-stimulated blood flow between impotent subjects with veno-sinusoidal leakage, in the absence of arterial disease, and a control group who achieved full erection with papaverine. It was therefore possible, by assessing the response to papaverine and measuring arterial blood flow, to distinguish between arterial insufficiency, veno-sinusoidal leakage and non-vascular causes of impotence. The method requires little skill and can be modified for use with inexpensive equipment.

Adult↗

The biochemical actions of phentolamine and papaverine on rat perfused skeletal muscle.

The direct actions of the vasodilators, papaverine and phentolamine, on skeletal muscle metabolism were investigated in an isolated perfusion system. Eviscerated male rats were hemisected above the diaphragm and perfused, via the aorta, with a physiological perfusion medium containing erythrocytes. Papaverine, but not phentolamine, reduced vascular resistance throughout the 80 min study. Papaverine caused marked reductions in muscle concentrations of ATP and phosphocreatine, when compared with muscle from preparations without added vasodilators. This was accompanied by elevations in lactate concentrations. Water content of papaverine-treated muscle was also higher than values in unperfused muscle taken in-vivo. Phentolamine, in contrast, had no effect on muscle ATP, phosphocreatine, lactate or water content. The metabolism of the entire preparation was also investigated. Papaverine induced increases in lactate output while phentolamine treatment caused an initial uptake, followed by an increased output of lactate. There was no significant effect of either papaverine or phentolamine on the metabolism of K+ and glucose. Arteriovenous differences in oxygen-saturation of haemoglobin and pH were also unaltered. Investigations on aspects of protein metabolism demonstrated that papaverine and phentolamine caused significant reductions in muscle protein synthesis when compared with control perfusions or in-vivo values. The reductions in synthesis were not due to reductions in cAMP or limitations in branched-chain amino acid supply. However, there was the suggestion that phentolamine caused a decrease in protein breakdown. The overall data indicated that papaverine and phentolamine may cause impairment of skeletal muscle metabolism. This has important implications for their therapeutic or experimental use.

Animals↗

Papaverine-sensitive vasospasm and arterial contractility and compliance after subarachnoid hemorrhage in dogs.

This study examined the relationship between papaverine-sensitive and -insensitive components of vasospasm, arterial contractility and compliance, and time after subarachnoid hemorrhage (SAH) in dogs. Eighteen dogs underwent angiography and then two intracisternal injections of blood. Angiography was repeated 4 (n = 5), 7 (n = 4), 10 (n = 4), or 14 (n = 5) days later. Papaverine, 100 to 200 mg, was infused into the basilar artery, and angiography was repeated. Four additional dogs had cerebral angiography only and served as controls. The basilar arteries were removed and studied pharmacologically. Significant vasospasm of the basilar artery was observed each time after SAH. Papaverine significantly reversed vasospasm at 4 and 7 days (88 +/- 6% and 63 +/- 11% of vasospasm reversed; analysis of variance, P < 0.05). The papaverine-insensitive component of vasospasm increased significantly with increasing time after SAH and with increasing severity of vasospasm. Arterial contractility and compliance decreased significantly with increasing time after SAH and were significantly related to the degree of papaverine-insensitive vasospasm but not to the severity of vasospasm. In conclusion, the majority of vasospasm early after SAH in dogs was caused by reversible vasoconstriction. The ability of papaverine to reverse vasospasm depended on the time after SAH and on the severity of vasospasm, a finding that may be important to the use of papaverine in humans. The pathological and biochemical basis for the association between papaverine-insensitive vasospasm and reduced arterial wall contractility and compliance remains to be determined.

Animals↗

Effects of morphine, clonidine and papaverine on synaptosomal 45Ca uptake and antinociceptive action in rats.

We studied the relationship between the inhibition of extracellular 45Ca2+ uptake into synaptosomes and the antinociceptive action induced by morphine, clonidine and papaverine in rats. The antinociceptive action induced by clonidine was as potent as that by morphine, but that by papaverine was less potent than those by morphine and clonidine. Antinociceptive action by morphine was considerably potentiated by the simultaneous administration of clonidine. However, the antinociceptive actions induced by morphine and clonidine were found to be mediated through different receptor mechanisms. Although the pretreatment by papaverine blocked the morphine-induced antinociception, the inhibition induced by papaverine was not found to be mediated through the opiate receptor because papaverine did not displace [3H]-dihydromorphine binding to the membrane fraction from rat brain. Papaverine also inhibited the antinociceptive action induced by clonidine. Morphine inhibited the veratrine-stimulated synaptosomal 45Ca2+ uptake by a naloxone-reversible process. Papaverine also strongly inhibited the veratrine-stimulated synaptosomal 45Ca2+ uptake, while clonidine had virtually no effect. The inhibition of synaptosomal 45Ca2+ uptake induced by morphine was not increased by simultaneous addition of clonidine. The strong inhibitions of synaptosomal 45Ca2+ uptake were still observed by simultaneous addition of papaverine with morphine and clonidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗

Inhibitory mechanism of papaverine on carbachol-induced contraction in bovine trachea.

We have demonstrated that the relaxing mechanism of papaverine in phasic muscles such as ileum, urinary bladder, and uterus is different from tonic muscles such as aorta. In this study, we examined the inhibitory mechanism of papaverine on carbachol (CCh)-induced contraction in the bovine trachea. Papaverine inhibited muscle contraction and increase in [Ca(2+)](i) level induced by CCh. Papaverine increased cAMP content but not cGMP content. Papaverine did not affect CCh-induced oxidized flavoproteins fluorescence or reduced pyridine nucleotides fluorescence. Papaverine (30 microM) remarkably inhibited muscle tension, but slightly decreased creatine phosphate and ATP contents. Iberiotoxin restored the inhibitions of muscle contraction and [Ca(2+)](i) level induced by papaverine or dibutyryl-cAMP. These results suggested that the relaxing mechanism of papaverine in the bovine trachea is mainly due to increases of cAMP content by inhibiting phosphodiesterase and the mechanism is partially involved in the activation of BK channel by cAMP.

Adenosine Triphosphate↗

Comparison of balloon angioplasty and papaverine infusion for the treatment of vasospasm following aneurysmal subarachnoid hemorrhage.

OBJECT: The purpose of this study was to test the hypothesis that balloon angioplasty is superior to papaverine infusion for the treatment of proximal anterior circulation arterial vasospasm following subarachnoid hemorrhage (SAH). Between 1989 and 1995, 125 vasospastic distal internal carotid artery or proximal middle cerebral artery vessel segments were treated in 52 patients. METHODS: Blood flow velocities of the involved vessels were assessed by using transcranial Doppler (TCD) monitoring in relation to the day of treatment with balloon angioplasty or papaverine infusion. Balloon angioplasty and papaverine infusion cohorts were compared based on mean pre- and posttreatment velocity at 24 and 48 hours using the one-tailed, paired-samples t-test. Balloon angioplasty alone was performed in 101 vessel segments (81%) in 39 patients (75%), whereas papaverine infusion alone was used in 24 vessel segments (19%) in 13 patients (25%). Although repeated treatment after balloon angioplasty was needed in only one vessel segment, repeated treatment following papaverine infusion was required in 10 vessel segments (42%) in six patients because of recurrent vasospasm (p < 0.001). Seven vessel segments (29%) with recurrent spasm following papaverine infusion were treated with balloon angioplasty. Although vessel segments treated with papaverine demonstrated a 20% mean decrease in blood flow velocity (p < 0.009) on posttreatment Day 1, velocities were not significantly lower than pretreatment levels by posttreatment Day 2 (p = 0.133). Balloon angioplasty resulted in a 45% mean decrease in velocity to a normal level following treatment (p < 0.001), a decrease that was sustained. CONCLUSIONS: Balloon angioplasty is superior to papaverine infusion for the permanent treatment of proximal anterior circulation vasospasm following aneurysmal SAH.

Adult↗

Efficacy of multiple intraarterial papaverine infusions for improvement in cerebral circulation time in patients with recurrent cerebral vasospasm.

OBJECT: Cerebral vasospasm that is caused by aneurysmal subarachnoid hemorrhage and that is refractory to maximal medical management can be treated with selective intraarterial papaverine infusions. The effects of single papaverine treatments on cerebral circulation time are well known. The purpose of this study was to assess the efficacy of multiple, repeated papaverine infusions on the cerebral circulation time in patients with recurrent vasospasm. METHODS: A retrospective study was conducted in 17 patients who received multiple intraarterial papaverine infusions in 91 carotid artery (CA) territories for the treatment of cerebral vasospasm. Cerebral circulation times were measured from the first angiographic image, in which peak contrast was seen above the supraclinoid internal CA, to the peak filling of cortical veins. Glasgow Outcome Scale (GOS) scores assessed 12 months after discharge were reviewed. Cerebral circulation times in 16 CA territories were measured in a control group of 11 patients. Seventeen patients received a total of 91 papaverine treatments. Prolonged cerebral circulation times improved after 90 (99%) of 91 papaverine treatments. The prepapaverine mean cerebral circulation time was 6.54 seconds (range 3.35-27 seconds) and the immediate postpapaverine mean cerebral circulation time was 4.19 seconds (range 2.1-12.6 seconds), an overall mean decrease of 2.35 seconds (36%, p < 0.001). Recurrent vasospasm reflected by prolonged cerebral circulation times continued to improve with subsequent papaverine infusions. Repeated infusions were just as successful quantitatively as the primary treatment (mean change 2.06 seconds). The mean cerebral circulation time in the control group was 5.21 seconds (range 4-6.8 seconds). In five patients a dramatic reversal of low-attenuation changes was detected on computerized tomography scans. The mean GOS score at 12 months after discharge was 3.4. CONCLUSIONS: The preliminary results indicate that multiple intraarterial papaverine treatments consistently improve cerebral circulation times, even with repeated infusions in cases of recurrent vasospasm.

Adult↗

Studies on gastroprotection induced by capsaicin and papaverine.

Capsaicin and papaverine are potent vasorelaxants with strong gastroprotective activity against damage induced by absolute ethanol. This protection was originally attributed to the increase in gastric mucosal blood flow (GBF) but the possibility that NO mediates the protective and hyperemic effects of capsaicin and papaverine has been little studied. Using N-nitro-L-arginine (L-NNA), a selective blocker of NO synthase, and L-arginine as a substrate for NO, we investigated the role of NO in protective action of capsaicin and papaverine against ethanol-induced gastric damage and in GBF. Pretreatment with capsaicin (0.1-0.5 mg/kg i.g.) or papaverine (0.1-2 mg/kg i.g.) reduced dose-dependently the area of ethanol-induced lesions, the LD50 being 0.3 and 1 mg/kg, respectively. This protection was accompanied by a gradual increase in the GBF. Intravenous (i.v.) injection of L-NNA (1.2-5 mg/kg), which by itself caused only a small increase in ethanol lesions, reversed dose-dependently the protective and hyperemic effects of capsaicin and papaverine against ethanol-induced damage and attenuated the increase in GBF induced by each of these agents alone. This deleterious effect of L-NNA on the gastric mucosa and the GBF was fully antagonized by L-arginine (200 mg/kg i.v.) but not by D-arginine. L-arginine partly restored the decrease in GBF induced by L-NNA. Pretreatment with indomethacin (5 mg/kg i.p.), which suppressed the generation of PG by 85%, slightly enhanced the mucosal lesions induced by ethanol but failed to affect the fall in GBF induced by this irritant. Gastroprotective and hyperemic effects of capsaicin and papaverine were partly reversed by indomethacin suggesting that endogenous PG are also implicated in these effects. Addition of L-NNA to indomethacin completely eliminated both the protective and hyperemic effects of capsaicin and papaverine. We conclude that both NO and PG contribute to the gastroprotective and hyperemic effects of capsaicin and papaverine on the gastric mucosa.

Animals↗

[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↗

[Influence of pH changes of the medium on relaxant actions of papaverine].

Influences of pH change in the medium on actions of papaverine were investigated in the intestinal smooth muscle of guinea pigs and compared with those of verapamil, a Ca2+ entry blocker. Papaverine contracted the ileal longitudinal muscle and inhibited the CaCl2-induced contraction of depolarized taenia coli. When the external pH was varied stepwise within the range of 6.8 to 7.6, both actions were equally facilitated with a lowering of the pH. A good correlation between these facilitated responses and the amount of ionized papaverine molecules was observed. Meanwhile, verapamil also induced the smooth muscle contraction and the inhibition of CaCl2-induced contraction. Although the dual action of verapamil were facilitated with a drop in the pH, the magnitudes of these facilitation were less than those of papaverine. Moreover, verapamil was less effective in inducing the smooth muscle contraction, but more potent in inhibiting the CaCl2-induced contraction, as compared to papaverine. These results indicate the possibility that ionized papaverine may displace bound calcium on the cell membrane of smooth muscle and this displacement may result in transient inward movement of Ca2+, leading to contraction and that subsequent blockade of Ca2+ entry by papaverine may block the contraction. These results also suggest that papaverine and verapamil may cause the dual action through a different mechanism.

Animals↗

[Topical application of papaverine for cerebral vasospasm using prolonged release pellet--experimental studies].

Possibility of prolonged-release pellets of papaverine in the treatment of cerebral vasospasm after subarachnoid hemorrhage was investigated. Papaverine hydrochloride was enclosed in silicone tubes or mixed with silicone elastomers and polymerized. The release rate of papaverine from the silicone tubes and elastomers into a saline solution was measured for 5 weeks at 37 degrees C and at room temperature. Although the volume of released papaverine was extremely large in the first two days, a constant release rate was maintained until the 35th day in vitro for both types of pellets. The daily amount of released papaverine was 1.5 to 3.0 x 10(-2)/day, and 1 to 4 x 10(-6)/day of original volume from silicone elastomers and tubes, respectively, at 37 degrees C. The release rate at 37 degrees C was 10 times as high as at room temperature. When the silicone elastomers were applied, the rate was well correlated with the surface area of the pellets, and was measured as 2.5 to 5.0 x 10(-5)/day/mm2 of the original volume. It means that when a pellet of 4 mm in diameter x 45 mm in length (a surface area of 600 mm2) is applied, 61.7% of the papaverine is released from the pellet during the first 2 weeks. Neither adverse reaction or intracranial histological abnormality was noted in vivo during the 40-day observation period using a dog, in which two pellets containing 275 mg and 297 mg of papaverine were subcutaneously implanted, and a pellet containing 275 mg of papaverine intracranially.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of papaverine on pancreatic exocrine secretion in the dog.

The effect of papaverine on the secretion of pancreatic juice in the dog was investigated in preparations of isolated, blood-perfused pancreas. Small doses of papaverine (1-30 microgram) injected intra-arterially did not induce any secretory action. Relatively large doses of papaverine (0.1-1 mg) caused dose-dependent increases in the secretion of pancreatic juice after a delay of a few minutes. The secretory activity of 1 mg of papaverine was approximately equal to that of 0.06 units of secretin. The concentration of bicarbonate in the pancreatic juice induced by papaverine was increased. However, protein concentration was increased slightly. This effect is analogous to that of secretin. Papaverine-induced secretion was not modified by pretreatment with phentolamine, propranolol, atropine, guanethidine and haloperidol. On the other hand, papaverine significantly potentiated the secretion of pancreatic juice induced by secretin. From these results, it is concluded that large doses of papaverine may produce an increase in pancreatic secretion mediated through the increase of intracellular cyclic AMP concentration.

Animals↗

[Endovascular treatment of cerebral vasospasm with intra-arterial papaverine infusion].

Thirty-one cases of cerebral vasospasm following subarachnoid hemorrhage were treated with intraarterial papaverine infusion. Symptomatic cases were nineteen, and asymptomatic cases were twelve. Papaverine (120 mg/saline 50 ml, 30 min) was injected superselectively to vasospastic vessels through a microcatheter. The rate of symptomatically improved cases was 63% initially, but about two thirds of those cases had recurrence within a day. The 63% of symptomatic cases showed infarction in spite of papaverine infusion. Three cases of recurrent vasospasm after intra-arterial papaverine underwent PTA and showed good dilatation of vasospastic vessels. The complications of our intra-arterial papaverine were hypotension in two cases, convulsion in one case and transient disturbed consciousness in one case. We experienced no fatal complications. Overall outcome was ADL1 (19%), ADL2 (25%), ADL3 (44%), ADL4 (0%), ADL5 (6%), and death (6%). Since the effect of intra-arterial papaverine infusion is of short duration and weak, combination of PTA and papaverine may be necessary. It is recommended to use papaverine for vasospasm in distal arteries such as M2, A1, A2, and to carry out PTA for proximal arteries such as ICA and M1.

Adult↗

Intraarterial papaverine infusion for cerebral vasospasm after subarachnoid hemorrhage.

PURPOSE: To evaluate the techniques and efficacy of intracranial intraarterial papaverine infusion for symptomatic vasospasm after subarachnoid hemorrhage caused by aneurysm rupture. METHODS: Papaverine was infused on 19 occasions in 14 patients, 6 hours to 2 days after spasm became apparent clinically. Sixty vascular territories were treated. Infusion was made into the supraclinoid internal carotid artery 20 times, cavernous internal carotid artery once, selective A1 anterior cerebral artery 8 times, M1 middle cerebral artery 7 times, and basilar artery 3 times. Papaverine doses ranged from 150 to 600 mg and exceeded 400 mg on 8 occasions. RESULTS: Angiographic improvement occurred in 18 (95%) of the 19 treatment sessions: results were excellent in 3 sessions, moderate in 8, and mild in 7. The best angiographic results often were obtained with superselective infusion, although angiographic results did not always correlate with clinical response. Seven (50%) of the 14 treated patients showed dramatic acute clinical improvement within 24 hours of papaverine therapy, and there was no clinical evidence of recurrent vasospasm in these patients. Recurrence of angiographic vasoconstriction was demonstrated in three patients; one showed marked clinical improvement after a second treatment. There were no episodes of systemic hypotension in any of the cases. Monocular blindness developed in one patient because of papaverine infusion near the ophthalmic artery. CONCLUSIONS: Papaverine was effective in dilating narrowed arteries in most patients with symptomatic vasospasm caused by subarachnoid hemorrhage. This series showed encouraging clinical results with no recurrence of neurologic deterioration in those patients who responded well to papaverine. Superselective infusion appears to be indicated in some cases for adequate papaverine delivery.

Adult↗

Papaverine inhibits bile acid excretion in isolated perfused rat liver.

We investigated the effects of papaverine on bile acid excretion into bile in the presence of infusions of taurocholic acid, tauroursodeoxycholic acid, taurochenodeoxycholic acid and taurodehydrocholic acid in a single-pass, isolated perfused rat liver model. Although continuous infusion of papaverine (1.6 mumol/min) did not reduce bile acid excretion in the presence of low-dose (1.0 mumol/min) infusions of taurocholic acid or tauroursodeoxycholic acid, papaverine significantly inhibited biliary excretion of bile acids in the presence of low-dose taurochenodeoxycholic acid (-50%) and high-dose (3.0 mumol/min) taurocholic acid (-54%), tauroursodeoxycholic acid (-37%) and taurodehydrocholic acid (-31%). During continuous infusion of taurocholic acid (3 mumol/min), a 15-min infusion of papaverine (3.2 mumol/min) reduced bile acid excretion significantly; however, total uptake of bile acid was slightly decreased by the papaverine infusion. Bile acid excretion increased over the baseline value after the papaverine infusion was stopped and then returned to baseline. These results suggest that papaverine does not affect the uptake phase of bile acids at the sinusoidal membrane but may affect the intracellular transport phase or the excretory phase at the bile canalicular membrane. When taurocholic acid was infused at a constant rate of 3 mumol/min for 20 min without papaverine and then stopped, bile acid excretion decreased gradually and was nearly zero by 52 min. Cumulative bile acid excretion in the 52 min after the end of the infusion reached 3.3 +/- 0.2 mumol/gm liver and represented the storage capacity of the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ventricular arrhythmia due to intracoronary papaverine: analysis of QT intervals and coronary vasodilatory reserve.

Intracoronary papaverine commonly produces striking QT interval prolongation with rare but serious ventricular dysrhythmias reported. Because of 3 cases of severe papaverine-induced dysrhythmia in our laboratory, QT intervals and hemodynamic and intracoronary velocity data collected during intracoronary papaverine administration were retrospectively reviewed in 34 patients; 20 patients with angiographically normal coronary arteries (group 1) and 14 patients (group 2) before and (group 2) after single-vessel left coronary angioplasty. QT intervals increased from 394 +/- 44 to 464 +/- 73 msec, 414 +/- 47 to 504 +/- 95 msec, and 410 +/- 41 to 486 +/- 75 msec for groups 1 and 2 before and after angioplasty, respectively (all P less than 0.01). There was no correlation with hemodynamic, electrocardiographic, or coronary vasodilatory reserve responses and change in QTc interval. In the 3 index patients having significant papaverine-related arrhythmias, a baseline QT interval was prolonged (after prior papaverine exposure) in only 1 in association with torsade de pointes. These data indicate that QT interval prolongation after papaverine is a common occurrence, but that the production of ventricular dysrhythmia is probably idiosynchratic in origin. In view of these findings, we recommend that appropriate antiarrhythmic preparations be in place for patients receiving intracoronary papaverine.

Adult↗

The effect of papaverine on acute opiate withdrawal in guinea pig ileum.

In the present work the effect of papaverine, a non specific smooth muscle relaxant, was investigated on the naloxone-precipitated withdrawal contracture of the acute morphine-dependent guinea-pig ileum in vitro. Furthermore, the effect of papaverine was also considered on DAGO (highly selective mu -agonist) and U50-488H (highly selective k-agonist) withdrawal to test whether the possible interaction of papaverine on opioid withdrawal involves mu - and/or k-opioid receptors. Following a 4 min in vitro exposure to opioid agonist, the guinea-pig isolated ileum exhibited a strong contracture after the addition of naloxone. Papaverine treatment (1 x 10(-7) - 5 x 10(-7) - 1 x 10(-6) M) before or after the opioid agonists was able of both preventing and reversing the naloxone-induced contracture after exposure to mu (morphine and DAGO) or k (U50-488H) opiate agonists in a concentration-dependent fascion. Both acetylcholine response and electrical stimulation were not affected by papaverine treatment whereas the final opiate withdrawal was still reduced. The results of the present study indicate that papaverine was able to produce significative influence on the opiate withdrawal in vitro and papaverine was able to exert its effect both at mu and k opioid agonists.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗