Papaverine

375.85

339.39

312930

200-502-1

DAA13NKG2Q

136630

DTXSID4023418

C726

White prisms from alcohol-diethyl ether; needles from petroleum ether|Triboluminescent, orthorhombic prisms from alcohol + ether|White crystalline powder

A - Alimentary tract and metabolism|G - Genito urinary system and sex hormones

2933499090

49.81000

4.66200

white powder

d420 1.337

147.5 °C

483.2ºC at 760mmHg

172.2ºC

1.6250 (estimate)

H2O: 25 mg/mL

Store in tight, light-resistant container as defined in the USP-NF. This material should be handled and stored per label instructions to ensure product integrity.

2.33X10-8 mm Hg at 25 deg C (est)

LD50 orl-rat: 325 mg/kg ARZNAD 20,1338,70

Optimal pH for storage of papverine solutions: 2.0-2.8

Henry's Law constant = 7.51X10-13 atm-cu m/mol at 25 °C (est)

pKa = 8.07 at 25 °C

185.3 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]|186.5 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated]

Monoclinic rods from water, mp 220-225 °C. UV max (ethanol) 249-250, 280-282, 311 nm (log E 4.69, 3.80, 3.82). One gram dissolves in about 40 mL water. Soluble in alcohol and chloroform. Practically insoluble in ether. pH of 0.05 molar solution 3.9; pH pf 2% aqueous solution 3.3 /Papverine hydrochloride/|White crystals or crystalline powder. One gram dissolves in about 30 mL of water and 120 mL of alcohol; practically insoluble in ether. ... injection, USP, is clear, colorless to pale-yellow solution /Papaverine hydrochloride/|Light yellow, crystalline powder; slightly soluble in water or alcohol; freely soluble in chloroform, acetone. /Papaverine nitrate/|Hydroxyl radical reaction rate constant = 1.91X10-10 cu cm/molec-sec at 25 °C (est)

II

6.1(a)

UN 1544 6.1/PG 3

1

22

22

NW8575000

Xn

SENSITIVE TO LIGHT & MOISTURE /papaverine/

P264, P270, P301+P312, P330, P501

H302

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.

|Warning|H302: Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P301+P312, P330, and P501|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|Aggregated GHS information provided by 6 companies from 1 notifications to the ECHA C&L Inventory.

Use a NIOSH approved respirator, if it is determined to be necessary by an industrial hygiene survey involving air monitoring. In the event that a respirator is not required, an approved dust mask should be used.|Engineering controls such as exhaust ventilation are recommended.

As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.|Water spray, dry chemical, carbon dioxide or foam as appropriate for surrounding fire and materials.

Wear approved respiratory protection, chemically compatible gloves and protective clothing. Wipe up spillage or collect spillage using a high-efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately-labelled container for disposal. Wash spill site.

Chemically compatible gloves. Safety glasses or goggles. Protect exposed skin.|As a general rule, when handling USP Reference Standards avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling.|This material is assumed to be combustible. As with all dry powders it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.

Papaverine was detected, not quantified in poppy tea generally brewed from the seeds, pods, and/or straw of the opium poppy (Papver somniferum), an annual that grows in Mexico, South America, Southeast and SouthwestAsia(1).

The effects of different concentrations of beta-cyclodextrin (beta-CyD), hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and 2,6-di-O-methyl-beta-cyclodextrin (DM-beta-CyD) on percutaneous absorption of papaverine hydrochloride (PAP) were investigated. Abdominal rat skin mounted in Franz cells was used for in vitro experiments. To evaluate CyD interaction with a bilayer structure model, dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and DPPC-Chol (8:2 mole ratio) vesicles were used. CyD vesicle interaction was evaluated by differential scanning calorimetry. Permeation through rat skin and calorimetric experiments demonstrated that at low concentrations DM-beta-CyD shows higher enhancer activity as a possible result of a perturbing action on the skin by a complexation of its lipid components, but at higher concentrations HP-beta-CyD is the most effective. By considering that HP-beta-CyD presents a very moderate destabilizing action on the skin, /it was concluded/ that a 10% aqueous solution of this macrocycle appears to be the most suitable transdermal absorption enhancer for PAP.|...The effect of papaverine ... 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 fashion. Both acetylcholine response and electrical stimulation were not affected by papaverine treatment whereas the final opiate withdrawal was still reduced. The results ... indicate that papaverine was able to influence the opiate withdrawal in vitro and papaverine was able to exert its effect both at mu and k opioid agonists.|/Investigators sought/ to determine the influences of papaverine and buffered papaverine on passage of dexamethasone administered intratympanically to the inner ear. Twenty-seven Vienna white rabbits were divided into five groups: eight received intratympanic dexamethasone (4 mg/mL) (group 1), seven received intratympanic papaverine (10 mg/mL) + dexamethasone (2 mg/mL) (group 2), six received buffered (with sodium bicarbonate 8.4%) intratympanic papaverine (7.5 mg/mL) + dexamethasone (1.5 mg/mL) (group 3), three had basal cortisol levels in venous blood and perilymph measured (group 4), and three received intravenous papaverine + dexamethasone (group 5). At 1 hr after the administration of the drugs, dexamethasone levels in ipsilateral and contralateral perilymph and venous blood were measured by radioimmunoassay. Animals in group 3 demonstrated the highest levels of ipsilateral perilymph dexamethasone. Ipsilateral perilymph levels were significantly higher in groups 1 and 3 than they were in the other groups (p<0.05). Although the perilymph levels observed in animals in group 2 were slightly higher than those in group 4, no significant difference existed (p = 0.160). /It was concluded/ that when papaverine is intratympanically administered together with dexamethasone after buffering, passage of dexamethasone to the inner ear is increased.|.../Investigators studied/ the combined effect of various cAMP reagents on LNCaP human prostate carcinoma cells. Papaverine and prostaglandin E2 (PGE2), combined synergistically induced morphological changes. Electron microscope study suggested that cells treated with both reagents become like neuroendocrine cells. The effect of both reagents on proliferation and malignancy of LNCaP cells /was then investigated/. The malignancy of cells was analyzed by soft agar colony-forming assay and an in vitro invasion assay. Proliferation and malignancy of LNCaP cells treated with both reagents were significantly decreased in comparison to the proliferation and malignancy of untreated cells. Furthermore, the expression of oncogenes such as c-myc and Bcl-2 was suppressed in differentiated LNCaP cells. These results suggest that papaverine combined with PGE2 can synergistically induce neuronal differentiation as well as decrease the malignancy of human prostatic cancer LNCaP cells.|For more Interactions (Complete) data for PAPAVERINE (12 total), please visit the HSDB record page.

LD50 Mouse intradermal 150 mg/kg|LD50 Mouse intramuscular 175 mg/kg|LD50 Mouse intravenous 25 mg/kg|LD50 Mouse intravenous 27.5 mg/kg|For more Non-Human Toxicity Values (Complete) data for PAPAVERINE (16 total), please visit the HSDB record page.

... Use of papaverine in patients with Parkinson's diease should probably be avoided, particularly if the patients are receiving levodopa.|It is not known whether papaverine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Papaverine Hydrochloride should be given to a pregnant woman only if clearly needed.|Vasoactive therapy for impotence should not be used in patients who might have conditions predisposing to priapism (e.g., sickle cell anemia or trait, multiple myeloma, leukemia), in those with anatomic deformation of the penis (e.g., angulation, cavernosal fibrosis, Peyronie's disease), or in men for whom sexual activity is inadvisable or contraindicated. In addition, vasoactive therapy should be discontinued in any patient who develops penile angulation, cavernosal fibrosis, or Peyronie's disease during therapy with the drug. ... Patients with penile implants should not be treated with vasoactive therapy for impotence.

~90%

Papaverine has been detected in various poppy species (Papaver sp.) and Indian snakeroot (Rauvolfia serpentina)(1).

Papaverine's production and adminstration as a vasodialator(1) and drug of abuse(2) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), a log Koc of 5.18(2), corresponding to a Koc of 151,365(SRC), indicates that papaverine is expected to have moderate mobility in soil(SRC). The pKa of papaverine is 8.07(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of papaverine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.5X10-13 atm-cu m/mole(SRC), using a fragment constant estimation method(5). Papaverine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.3X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(6). Biodegradation data in soil were not available(SRC, 2012).|AQUATIC FATE: Based on a classification scheme(1), a log Koc of 5.18(2), corresponding to a Koc of 151,365(SRC), indicates that papaverine is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 7.5X10-13 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4) According to a classification scheme(5), an estimated BCF of 41(SRC), from its log Kow of 2.95(6) and a regression-derived equation(7) suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Biodegradation data in water were not available(SRC, 2012).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), papaverine, which has an estimated vapor pressure of 2.3X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase papaverine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 0.7 hours(SRC), calculated from its rate constant of 1.9X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase papaverine may be removed from the air by wet or dry deposition(SRC). Papaverine absorbs light at wavelengths as high as 327 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of papaverine with photochemically-produced hydroxyl radicals has been estimated as 1.9X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 0.7 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Papaverine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). Papaverine absorbs light at wavelengths as high as 327 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 41 was calculated in fish for papaverine(SRC), using a log Kow of 2.95(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC).

A log Koc of 5.18 has been reported for papaverine(1), corresponding to a Koc of 151,365(SRC). According to a classification scheme(2), this estimated Koc value suggests that papaverine is expected to be immobile in soil. The pKa of papaverine is 8.07(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). A Kd of 5442 has been reported using an agricultural soil from Corrstown, Co. Dublin, Ireland(1).

The Henry's Law constant for papaverine is estimated as 7.5X10-13 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that papaverine is expected to be essentially nonvolatile from water or moist soil surfaces(2). Papaverine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.3X10-8 mm Hg(SRC), determined from a fragment constant method(3).

While data specific to papaverine were not located(SRC, 2012), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 563 workers (481 of these were female) were potentially exposed to papaverine in the US(1). Occupational exposure to papaverine may occur through inhalation and dermal contact with this compound at workplaces where papaverine is produced or administered. Exposure to papaverine among the general population may be limited to those administered the drug as a vasodialator and those involved in illegal production and abuse of this substance(SRC).

For the treatment of impotence and vasospasms.

/EXPERIMENTAL THER:/ The present study evaluates whether intrathecal papaverine induces changes in spinal cord blood flow (SCBF) of injured spinal cord and prevents secondary injury. After laminectomy was performed and contusive spinal cord injuries were induced in adult female Macaca rhesus, three received intrathecal papaverine, and three received saline 0.9% for control. ... Mean arterial blood pressure showed no significant change in both groups. In the papaverine group, SCBF recovered to 81.35+/-7.8% of baseline at 15 min, 75.24+/-6.3% at 30 min, 73.38+/-2.3% at 90 min and 72.57+/-4.1% at 180 min after the completion of infusion. SCBF was significantly higher than the control groups (P<0.01). There was no occlusion of the arteries, but occluded veins were identified at the injured site. The MVD in the spinal cord of the control group was significantly lesser than the papaverine group (P<0.01). Luxol Fast Blue staining showed that intrathecal papaverine reduced myelin loss in the lesion 2 weeks after injury (P<0.05). Intrathecal administration of papaverine increased SCBF in non-human primates. It is likely that the effects of papaverine can reduce secondary injury in spinal cord injured Macaca rhesus.|/EXPERIMENTAL THER:/ To find an effective method for the treatment of malignant cerebral glioma by opening the blood-brain-barrier (BBB). The concentration of methotrexate (MTX) in tumor was measured in 18 patients with cerebral glioma, and 155 patients with malignant glioma were treated by intracarotid infusion of papaverine and Bis-chloronitrosourea (BCNU). After intracarotid infusion of papaverine for reversible opening of BBB, the MTX concentration in tumor tissue was 1810 +/- 380 ng/g, higher than that in patients without papaverine infusion (997 +/- 126 ng/g). Eighty-nine patients with glioblastoma and 66 patients with anaplastic astrocytoma received intracarotid infusion of papaverine and BCNU (250 mg) for an average of 2.14 times. The mean survival time of these patients was 114.5 weeks, median survival time was 140 weeks, and five-year survival rate was 22.97%. The combined chemotherapy with papaverine and BCNU through intra-arterial infusion is simple, safe and effective in treating malignant cerebral glioma so long as the tumor is sensitive to the drugs.|/EXPERIMENTAL THER:/ /Investigators sought to assess/ 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. /Investigators/ 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. ...|/EXPERIMENTAL THER:/ /Investigators/ tested the hypothesis that the continuous infusion of papaverine-containing solutions in peripheral arterial catheters would decrease the catheter failure rate and increase the functional duration of the catheter in neonates. In a prospective, randomized, placebo-controlled, masked trial, 82 catheters were placed in 70 neonates in the papaverine group and 98 catheters were placed in 71 neonates in the placebo group. The catheters in the papaverine group remained functional for a significantly longer duration than those in the placebo group. The median (25th%, 75th%) time before catheter failure was 16.6 (9.5, 24.3) days in the papaverine group and 12 days (6.1, 18.2) in the placebo group ( P = .023; Cox proportional hazards model). There was no significant difference in the incidence of intraventricular hemorrhage (IVH) between groups, and there was no evidence of hepatic toxicity. The continuous infusion of papaverine-containing fluids prolongs the patency of peripheral arterial catheters in neonates. In this small number of infants, /there was/ no difference in the incidence of IVH or hepatic toxicity.|For more Therapeutic Uses (Complete) data for PAPAVERINE (32 total), please visit the HSDB record page.

Intra-arterial papaverine (IAP) is used to treat symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH). IAP, however, can increase intracranial pressure (ICP). In this study, /investigators/ examined whether IAP alters brain oxygen (BtO2). Poor clinical grade (Hunt & Hess IV or V) SAH patients who underwent continuous ICP and BtO2 monitoring during IAP infusion for symptomatic cerebral vasospasm were evaluated as part of a prospective observational study. ... IAP infusion to treat cerebral vasospasm following SAH can increase ICP and reduce BtO2. The IAP-induced reduction in BtO2 may help explain why IAP, although it reverses arterial narrowing, does not improve patient outcome.|Hepatitis, probably related to an immune mechanism, has been reported infrequently. Rarely, this has progressed to cirrhosis.|The following side effects have been reported: general discomfort, nausea, abdominal discomfort, anorexia, constipation or diarrhea, skin rash, malaise, vertigo, headache, intensive flushing of the face, perspiration, increase in the depth of respiration, increase in heart rate, a slight rise in blood pressure, and excessive sedation.|It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when papaverine hydrochloride is administered to a nursing woman.|For more Drug Warnings (Complete) data for PAPAVERINE (15 total), please visit the HSDB record page.

Papaverine is a nonxanthine phosphodiesterase inhibitor for the relief of cerebral and peripheral ischemia associated with arterial spasm and myocardial ischemia complicated by arrhythmias. The main actions of Papaverine are exerted on cardiac and smooth muscle. Like qathidine, Papaverine acts directly on the heart muscle to depress conduction and prolong the refractory period. Papaverine relaxes various smooth muscles. This relaxation may be prominent if spasm exists. The muscle cell is not paralyzed by Papaverine and still responds to drugs and other stimuli causing contraction. The antispasmodic effect is a direct one, and unrelated to muscle innervation. Papaverine is practically devoid of effects on the central nervous system. Papaverine relaxes the smooth musculature of the larger blood vessels, especially coronary, systemic peripheral, and pulmonary arteries.

Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases. (See all compounds classified as Phosphodiesterase Inhibitors.)|Drugs used in the treatment of urogenital conditions and diseases such as URINARY INCONTINENCE; PROSTATIC HYPERPLASIA; and ERECTILE DYSFUNCTION. (See all compounds classified as Urological Agents.)|Drugs used to cause dilation of the blood vessels. (See all compounds classified as Vasodilator Agents.)

It is not known whether this drug is excreted in human milk.|Papaverine is effective by all routes of administration. A considerable fraction of the drug localizes in fat deposits and in the liver, with the remainder being distributed throughout the body. It is metabolized in the liver. About 90% of the drug is bound to plasma protein. Although estimates of its biologic half-life vary widely, reasonably constant plasma levels can be maintained with oral administration at 6 hour intervals. The drug is excreted in the urine in an inactive form.|... In vitro autoradiography studies of rat and monkey brain sections revealed selective binding of (11)C-papaverine to PDE10A enriched regions: the striatum of rat brain and the caudate and putamen of rhesus monkey brain. The biodistribution of (11)C-papaverine in rats at 5 min demonstrated an initially higher accumulation in striatum than in other brain regions, however the washout was rapid. MicroPET imaging studies in rhesus macaques similarly displayed initial specific uptake in the striatum with very rapid clearance of (11)C-papaverine from brain. ...|Absorption: Slowly released into venous circulation; minimal, if any, systemic effects. /Papaverine, intracavernosal/|For more Absorption, Distribution and Excretion (Complete) data for PAPAVERINE (7 total), please visit the HSDB record page.

Papaverine yielded demethylpapaverine in rabbit. Axelrod J, Biochem J (63) 634, 1956. /from table/|Papaverine hydrochloride is ... excreted in the urine, chiefly as glucuronide, conjugates of phenolic metabolites.|The drug is metabolized in the liver and is excreted mainly in the urine, primarily as metabolites. Less than 1% of /papaverine hydrochloride/ is excreted unchanged.

0.5-2 hours|Papaverine /hydrochloride/ has an elimination half-life of 0.5-2 hours..

Perhaps by its direct vasodilating action on cerebral blood vessels, Papaverine increases cerebral blood flow and decreases cerebral vascular resistance in normal subjects; oxygen consumption is unaltered. These effects may explain the benefit reported from the drug in cerebral vascular encephalopathy.|... In this study, /investigators/ 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 uM) 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.|With large overdoses, papaverine is a potent inhibitor of cellular respiration and a weak calcium-channel blocking agent.|To characterize the effects of papaverine on HERG channels expressed in Xenopus oocytes as well as cardiac action potential in rabbit ventricular myocytes. Conventional microelectrodes were used to record action potential in rabbit ventricular myocytes. HERG currents were recorded by 2-electrode voltage clamp technique in Xenopus oocytes injected with HERG cRNA. Papaverine increased the cardiac action potential duration in rabbit ventricular myocytes. It blocked heterologously-expressed HERG currents in a concentration-dependent manner (IC50 71.03+/-4.75 umol/L, NH 0.80, n=6), whereas another phosphodiesterase inhibitor, theophylline (500 umol/L), did not. The blockade of papaverine on HERG currents was not voltage-dependent. The slope conductance measured as a slope of the fully activated HERG current-voltage curves decreased from 78.03+/-4.25 muS of the control to 56.84+/-5.33, 36.06+/-6.53, and 27.09+/-5.50 uS (n=4) by 30, 100, and 300 umol/L of papaverine, respectively. Papaverine (100 umol/L) caused a 9 mV hyperpolarizing shift in the voltage-dependence of steady-state inactivation, but there were no changes in the voltage-dependence of HERG current activation. Papaverine blocked HERG channels in the closed, open, and inactivated states. These results showed that papaverine blocked HERG channels in a voltage- and state-independent manner, which may most likely be the major mechanism of papaverine-induced cardiac arrhythmia reported in humans.|...To identify the role of potassium and calcium channels in papaverine-induced vascular relaxation, ... the effect of papaverine on potassium and calcium channels in freshly isolated smooth muscle cells from rat basilar artery /was examined/. The isolation of rat basilar smooth muscle cells was performed by special techniques. The whole cell currents were recorded by whole cell patch clamp technique in freshly isolated smooth muscle cells from rat basilar artery. Papaverine was added to the bath solution. Papaverine of 100 uM into bath solution increased the amplitude of the outward K(+) current which was completely blocked by BKCa blocker, IBX (iberiotoxin) and a calcium chelator, BAPTA (1,2-bis(o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid) in whole cell mode. Papaverine (100 uM) also inhibited L type Ca(2+) current recorded in isolated smooth muscle cells from rat basilar artery. These results strongly suggest that Ca(2+)-activated potassium channels and L type Ca(2+) channels may be involved in papaverine-induced vascular relaxation in rat basilar artery.|For more Mechanism of Action (Complete) data for PAPAVERINE (18 total), please visit the HSDB record page.

Forced diuresis, peritoneal dialysis, hemodialysis, or charcoal hemoperfusion have not been established as beneficial for an overdose of papaverine hydrochloride.|Protect the patient's airway and support ventilation and perfusion. Meticulously monitor vital signs, blood gases, blood chemistry values, and other variables. If convulsions occur, consider diazepam, phenytoin, or phenobarbital. If the seizures are refractory, general anesthesia with thiopental or halothane and paralysis with a neuromuscular blocking agent may be necessary. For hypotension, consider intravenous fluids, elevation of the legs, and an inotropic vasopressor, such as dopamine or norepinephrine (levarterenol). Theoretically, calcium gluconate may be helpful in treating some of the toxic cardiovascular effects of papaverine; monitor the ECG and plasma calcium concentrations.|... Appropriate measures for treatment of coma or respiratory depression and maintenance of blood pressure; hemodialysis may be useful.|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|For more Antidote and Emergency Treatment (Complete) data for PAPAVERINE (6 total), please visit the HSDB record page.

/HUMAN EXPOSURE STUDIES/ Papaverine is used for the evaluation of functional status of the coronary arteries but it may provoke severe ventricular tachyarrhythmias (VTAs). This study compared the clinical and ECG characteristic of patients with papaverine-induced VTAs. The study involved 25 patients who underwent a fractional flow reserve (FFR) study. FFR was determined as the ratio of blood pressure at the distal and the proximal site of stenosis after intracoronary papaverine administration at 12 mg into the left and 8 mg into the right coronary artery. The QT and QTU intervals were measured manually in the limb leads and in the precordial leads, respectively and corrected by the R-R interval to obtain QTc and QTUc. The clinical and ECG data were compared between the patient groups with and without VTAs. After papaverine administration into the left (20), right (3) or both coronary arteries (2), the RR interval shortened, but non-significantly however, the QT interval (and QTc) and the QTU interval (and QTUc) were significantly prolonged. VTAs developed in four women: torsade de pointes in 3 followed by ventricular fibrillation and ventricular premature beats in 1 patient. After papaverine administration, QTU and QTUc were more prolonged in women than men and in patients with VTAs compared to those without. Just prior to VTAs, giant T-U waves were observed. Intracoronary papaverine was used to determine FFR which may induce VTAs. VTAs developed only in women and they were closely related to prolongation of the QTU intervals with prominent T-U waves.|/HUMAN EXPOSURE STUDIES/ Fatalities have followed intravenous use. Polymorphous ventricular tachycardia with prolongation of the QT intervalhas followed infusion of 6 to 10 mg into the coronary arteries.|/HUMAN EXPOSURE STUDIES/ Doses as high as 1 g by mouth produce only minimal side effects. IV doses of 30 and 65 mg produced rapid demise of 2 adults preceded by hyperpnea, tachypnea and eventually apnea. Heart sounds were not audible after onset of respiratory symptoms. Death may have resulted from either cardiac or respiratory disturbance.|/SIGNS AND SYMPTOMS/ The symptoms of toxicity from papaverine hydrochloride often result from vasomotor instability and include nausea, vomiting, weakness, central nervous system depression, nystagmus, diplopia, diaphoresis, flushing, dizziness, and sinus tachycardia.|For more Human Toxicity Excerpts (Complete) data for PAPAVERINE (22 total), please visit the HSDB record page.

Cerespan

Artegodan, Cepaverin, Cerebid, Cerespan, Dynovas, Optenyl, Pameion, Panergon, Papital T.R., Pavabid, Pavacen, Pavadel, Pavagen, Pavakey, Pavased, Spasmo-Nit, Therapav, Vasal, Vasospan /Papverine hydrochloride/|Table: Papaverine Hydrochloride Preparations [Table#4480]

Analyte: Papaverine; matrix: solutions; procedure: high performance liquid chromatography with ultraviolet detection at 254 nm|Analyte: Papaverine; matrix: solutions; procedure: high performance liquid chromatography with ultraviolet detection at 220 nm|Analyte: Papaverine; matrix: solutions; procedure: high performance liquid chromatography with ultraviolet detection at 210 nm|For more Analytic Laboratory Methods (Complete) data for PAPAVERINE (21 total), please visit the HSDB record page.

Analyte: Papaverine; matrix: cells; procedure: high performance liquid chromatography with ultraviolet detection at 340 nm; limit of detection: 100-1000 ng/mL|Analyte: Papaverine; matrix: blood, urine; procedure: high performance liquid chromatography with ultraviolet detection at 251.1 nm|Analyte: Papaverine; matrix: urine, blood; procedure: high performance liquid chromatography with ultraviolet detection at 239 nm|Analyte: Papaverine; matrix: blood, urine; procedure: high performance liquid chromatography with ultraviolet detection at 239 nm; limit of detection at 25 ng/mL|For more Clinical Laboratory Methods (Complete) data for PAPAVERINE (8 total), please visit the HSDB record page.

Pharmaceuticals -> Animal Drugs -> Approved in Taiwan