Proflavine

209.252

209.25

208-515-4

CY3RNB3K4T

DTXSID9043776

Yellow needles from alcohol. Solutions are brownish and when diluted are fluorescent.

2933990090

64.9

1.4

Proflavine dihydrochloride is an orange-red to brown-red crystalline powder. pH (0.1% aqueous solution) 2.5-3.0.

1.1847 (rough estimate)

284-286 °C

506.9ºC at 760 mmHg

292.9ºC

1.833

1.04e-01 g/L

LD50 s.c. in mice: 0.14 g/kg (Rubbo)

8.06(at 20 °C)

8.06 (at 20 °C)|pKa = 9.7

Orange-yellow needles. pH of 0.1 percent soln 2.5-3.0 /Dihydrochloride/

P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, P501

H302

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 38 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 39 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

LD50 mouse intraperitoneal 50 mg/kg|LD50 mouse subcutaneous 140 mg/kg

A bioassay of the carcinogenicity of proflavine monohydrochloride hemihydrate was conducted using Fischer 344/CR rats and B6C3F1 mice. The compound was administered in the diet at concentrations of 300 and 600 ppm to groups of 50 rats for 109 weeks and at concentrations of 200 and 400 ppm to groups of 50 mice for 104 weeks. The animals were subjected to necropsy and histopathologic evaluation as they died or at the end of their periods of treatment. Average weights attained by high-dose groups were consistently lower than those of control groups; weights of low-dose groups showed essentially no differences from those of the controls. Survival rates of the treated rats and mice did not differ from those of the controls except for a lower rate among the female mice. Five malignant neoplasms of the intestinal tract consisting of three leiomyosarcomas of the small intestine, a sarcoma near the colon area, and an adenocarcinoma of the small intestine were observed in five of the high-dose male rats. None were observed in other treatment or control groups. If these five intestinal neoplasms are considered together, they aresignificant at the P=0.026 level using the Fisher exact test. A positive dose-related trend (P=0.034) was also present for the three leiomyosarcomas. The observed incidence of hepatocellular carcinoma in female mice was 4/50 (8%) in the control group, 20/49 (41%) in the low-dose group, and 22/50 (44%) in the high-dose group. The test for dose-related trend showed a level of significance of P<0.001. In male mice, the observed incidence of hepatocellular carcinoma was 20/49 (41%) in the control group 28/49 (57%) in the low-dose group, and 30/50 (60%) in the high-dose group. The dose-related trend was significant at P=0.057, and the high dose was significant at P=0.044. The unusually high incidence of hepatocellular carcinomas and hemangiosarcomas in control male mice and the unusually high incidence of malignant lymphomas in all groups of female mice in conjunction with the fact that a positive-control carcinogen was tested in the same room with these animals, raises a question of the validity of these bioassay results. /Proflavine monohydrochloride hemihydrate (CAS No. 952-23-8)/

Topical antiseptic used mainly in wound dressings.

/Exptl/ We used the photodynamic inactivation technique with proflavine as the photoactive dye to treat herpetic epithelial keratitis in a preliminary study of patients who had idoxuridine toxicity or resistance. A comparative study with idoxuridine in treating dendritic ulcerations of the cornea showed a good therapeutic effect. But the investigation was suspended when adverse reactions, consisting of a generalized epithelial keratitis and an anterior uveitis, possibly of phototoxic origin, developed in a few patients receiving treatment. The ulcers treated by photodynamic inactivation apparently healed by a process of "debridement" followed by subsequent re-epithelialization.|... Proflavine wool is used by many surgeons in the UK as a dressing that can be moulded to conform to the contours of a corrected prominent ear. ...

Proflavine allergy is uncommon, occurring in approximately 6% of patients attending contact dermatitis clinics. Proflavine wool is used by many surgeons in the UK as a dressing that can be moulded to conform to the contours of a corrected prominent ear. It may have bacteriostatic properties. We present a case where contact dermatitis in response to proflavine developed after pinnaplasty. This caused diagnostic confusion, a lengthened hospital stay and an unsightly hypertrophic scar.

Proflavine is an acriflavine derivative which is a disinfectant bacteriostatic against many gram-positive bacteria. Proflavine is toxic and carcinogenic in mammals and so it is used only as a surface disinfectant or for treating superficial wounds.

Substances used on humans and other animals that destroy harmful microorganisms or inhibit their activity. They are distinguished from DISINFECTANTS, which are used on inanimate objects. (See all compounds classified as Anti-Infective Agents, Local.)

The uptake of the fluorescent drug proflavine was measured in suspensions of hepatocytes from normal and carcinogen (2-acetylaminofluorine, AAF)-fed rats by flow cytometry. Drug uptake into hepatocytes from carcinogen-fed animals was consistently lower than that into hepatocytes from normal animals. Isolated nuclei, prepared from the livers of normal and AAF-fed rats showed similar proflavine uptake. Drug uptake into hepatocytes from AAF-fed animals, however, was increased by prior exposure to a metabolic inhibitor. Thus, differences in drug uptake may reflect changes in the cell membrane, together with an alteration in the metabolic integrity of the cells. The uptake of drug in hepatocytes from AAF-fed rats was uniformly low within each cell preparation. However, drug uptake varied not only between tumours arising in the livers of these animals but also within each tumour cell preparation. This study indicates that flow cytometry can provide an effective means for analysing drug uptake into cell populations arising during hepatocarcinogenesis.|1. The disposition of proflavine (PRO) and acriflavine (ACR) were examined in channel catfish after intravascular (i.v.) dosing (1 mg/kg) or waterborne exposure (10 mg/l for 4 h). 2. After i.v. dosing, plasma concentration-time profiles of parent PRO and ACR were best described by two- and three-compartment pharmacokinetic models respectively. Terminal elimination half-lives of PRO and ACR in plasma were 8.7 and 11.4 h respectively. 3. In animals dosed with 14C-PRO or 14C-ACR, total drug equivalent concentrations were highest in the excretory organs and lowest in muscle, fat and plasma. In PRO-dosed animals, residues in the liver and trunk kidney were composed primarily of glucuronosyl and acetyl conjugates of PRO; residues in muscle were composed mostly (> 95%) of the parent drug. In ACR-dosed animals, the parent compound comprised > 90% of the total residues in all tissues examined. 4. PRO and ACR were poorly absorbed in catfish during waterborne exposure. At the end of a 4-h exposure, parent PRO and ACR concentrations in muscle were 0.064 and 0.020 microgram/g respectively. Levels in muscle declined below the limit of determination (0.005 microgram/g) within 1-2 weeks.

Proflavine (3,6-diaminoacridine) has potential for use as an antiinfective in fish, and its metabolism by rainbow trout was therefore studied. Fourteen hours after intraarterial bolus administration of 10 mg/kg of proflavine, three metabolites were found in liver and bile, and one metabolite was found in plasma using reversed-phase HPLC with UV detection at 262 nm. Treatment with hydrochloric acid converted the three metabolites to proflavine, which suggested that the metabolites were proflavine conjugates. Treatment with beta-glucuronidase and saccharic acid 1,4-lactone, a specific beta-glucuronidase inhibitor, revealed that two metabolites were proflavine glucuronides. For determination of UV-VIS absorption and mass spectra, HPLC-purified metabolites were isolated from liver. Data from these experiments suggested that the proflavine metabolites were 3-N-glucuronosyl proflavine (PG), 3-N-glucuronosyl,6-N-acetyl proflavine (APG), and 3-N-acetylproflavine (AP). The identities of the metabolites were verified by chemical synthesis. When synthetic PG and AP were compared with the two metabolites isolated from trout, they had the same molecular weight as determined by matrix-assisted, laser desorption ionization, time-of-flight MS. In addition, they coeluted on HPLC under different mobile phase conditions. Finally, the in vitro incubation with liver subcellular preparations confirmed this characterization and provided the evidence that APG can be formed by glucuronidation of AP or acetylation of PG.|A liquid chromatographic (LC) method was developed for determination of acriflavine (ACR) and proflavine (PRO) residues in channel catfish muscle. Residues were extracted with acidified methanol solution, and extracts were cleaned up with C18 solid-phase extraction columns. Residue concentrations were determined on an LC cyano column, with spectrophotometric detection at 454 nm. Catfish muscle was individually fortified with ACR (purified from commercial product) and PRO at concentrations of 5, 10, 20, 40, and 80 ppb (5 replicates per level). Mean recoveries from fortified muscle at each level ranged from 86 to 95%, with relative standard deviations (RSDs) of 2.5 to 5.7%. The method was applied to incurred residues of ACR and PRO in muscle after waterborne exposure of channel catfish to commercial acriflavine (10 ppm total dye for 4 h). RSDs for incurred residues of ACR and PRO were in the same range as those for fortified muscle. Low residue concentrations (< 1% of exposure water concentration) suggested poor absorption of ACR and PRO in catfish.

Proflavine acts by interchelating DNA (intercalation), thereby disrupting DNA synthesis and leading to high levels of mutation in the copied DNA strands. This prevents bacterial reproduction.|The ability of proflavine (3,6-diaminoacridine) and its 2,7-dimethyl, 2,7-diethyl, 2,7-diisopropyl and 2,7-di-tert.-butyl derivatives to induce the 'petite' mutation in Saccharomyces cerevisiae has been studied in relation to the DNA-binding properties of the compounds. The nature of the binding has been investigated by nuclear magnetic resonance techniques, and the results support and clarify earlier suggestions that the first 3 members of the series intercalate into DNA while the diisopropyl and di-tert.-butyl compounds do not. Toxicity of the drugs was primarily associated with their mode of DNA binding, but lipophilicity had an important secondary effect. It seems likely that the toxic properties of the more lipophilic DNA-intercalating members of the series mask their potential for 'petite' mutagenesis.|The toxicities of several aminoacridines were measured against pathogenic strains of both Gram-positive (Staphylococcus aureus, Enterococcus faecalis, Bacillus cereus) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) organisms. In several cases, illumination at a light dose of 6.3 J/cm2 resulted in considerable decreases in the minimum lethal drug concentrations required, giving up to 50-fold increases in bactericidal activity. Derivatives of 9-aminoacridine (aminacrine) exhibited phototoxicity against one or more of the test organisms, but the established photosensitizing acridines proflavine and acridine orange were photobactericidal against all strains.

/SRP:/ Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

/SPECIAL STUDIES/ The induction of unscheduled DNA synthesis (UDS) and the alteration of semiconservative DNA replication by the structurally related intercalating agents proflavine and 9-aminoacridine were studied in MRC-5 human fibroblasts in culture ... Proflavine affected DNA synthesis, but did not elicit any UDS.

3,6 Diamino Acridine

3,6-Acridinediamine: INACTIVE