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Biomedical subjects

M E Rosenthale

Publications and source records attributed to M E Rosenthale.

At least 19 recordsLinked to original sources
PubMed1994

Tepoxalin: a dual cyclooxygenase/5-lipoxygenase inhibitor of arachidonic acid metabolism with potent anti-inflammatory activity and a favorable gastrointestinal profile.

Tepoxalin [5-(4-chlorophenyl)-N-hydroxy-(4-methoxyphenyl)-N-methyl-1H- pyrazole-3-propanamide] is a potent inhibitor of sheep seminal vesicle cyclooxygenase (CO) (IC50 = 4.6 microM), rat basophilic leukemia cell (RBL-1) lysate CO (IC50 = 2.85 microM) and CO from intact RBL-1 cells (IC50 = 4.2 microM). The compound inhibits the production of thromboxane B2 (TxB2) in Ca++ ionophore A-23187-stimulated human peripheral blood leukocytes (HPBL; IC50 = 0.01 microM) and human whole blood (IC50 = 0.08 microM) and is a potent inhibitor of epinephrine-induced human platelet aggregation (IC50 = 0.045 microM). Tepoxalin inhibits lipoxygenase (LO) in RBL-1 lysates (IC50 = 0.15 microM) and intact RBL-1 cells (IC50 = 1.7 microM) and inhibits the generation of leukotriene B4 (LTB4) in calcium ionophore A-23187-stimulated HPBL (IC50 = 0.07 microM) and human whole blood (IC50 = 1.57 microM). Human platelet 12-LO (IC50 = 3.0 microM) is inhibited, but 15-LO is only weakly so (IC50 = 157 microM). In vivo, tepoxalin, administered orally, demonstrated potent anti-inflammatory activity in the established adjuvant arthritic rat (ED50 = 3.5 mg/kg) and potent analgesic activity in the acetic acid abdominal construction assay in mice (ED50 = 0.45 mg/kg). In an ex vivo whole blood eicosanoid production assay, tepoxalin produces a dose-related inhibition of prostaglandin (PG) and LT production in dogs (PGF2 alpha - ED50 = 0.015 mg/kg; LTB4 - ED50 = 2.37 mg/kg) and adjuvant arthritic rats following oral administration. In adjuvant arthritic rats, tepoxalin is devoid of ulcerogenic activity within its anti-inflammatory therapeutic range (1-33 mg/kg p.o.) and does not exhibit ulcerogenic activity in normal rats at doses lower than 100 mg/kg (UD50 = 173 mg/kg p.o.). Tepoxalin represents a new class of anti-inflammatory drugs which may exhibit less gastrointestinal toxicity and may be efficacious in immunoinflammatory disease states where excessive PG and LT production has been implicated and may offer a significant alternative to nonsteroidal and corticosteroidal anti-inflammatory therapy.

Animals↗
PubMed1992

In vitro and in vivo antibacterial activities of levofloxacin (l-ofloxacin), an optically active ofloxacin.

The antibacterial activity of levofloxacin was compared with those of ofloxacin, ciprofloxacin, and other antibiotics. In general, levofloxacin was equally active or up to fourfold more active than ofloxacin against all 801 organisms tested. Levofloxacin was twofold [corrected] more active than ciprofloxacin against Streptococcus pneumoniae and 2- to 4-fold more active than ciprofloxacin against Staphylococcus aureus, Xanthomonas maltophilia, and Bacteroides fragilis. Levofloxacin was two- to eightfold more active than ciprofloxacin against coagulase-negative staphylococci and Acinetobacter spp., although these improvements in potency may not be clinically relevant. Levofloxacin inhibited 90% of streptococci when it was used at concentrations of 1 to 2 micrograms/ml. Levofloxacin was two- to fourfold less active than ciprofloxacin against most members of the family Enterobacteriaceae, such as Escherichia coli; Klebsiella pneumoniae; Citrobacter, Proteus, Providencia, Salmonella, and Yersinia spp.; and Pseudomonas aeruginosa. Both compounds were equally active against Pseudomonas cepacia. The in vitro DNA gyrase inhibitory activity of levofloxacin was as potent as that of ciprofloxacin, with a 50% inhibitory concentration of 0.65 micrograms/ml against an E. coli enzyme. In vivo, oral treatment with levofloxacin was as efficacious or more efficacious than that with ciprofloxacin in systemic as well as pyelonephritis infections in mice. Levofloxacin achieved higher concentrations in the serum and tissue of mice than did ciprofloxacin. This study presents some potential advantages of the pure L isomer of ofloxacin over ciprofloxacin and other quinolones.

Animals↗
PubMed1991

Protein kinase C independent restoration of specific immune responsiveness in common variable immunodeficiency.

7,8-Disubstituted guanine ribonucleosides represent a class of B lymphocyte agonists that utilize a protein kinase C-independent signaling pathway. These compounds provide an alternate T helper signal for B cells and enhance antigen-specific humoral responses in the murine model and in an IL-2-dependent human model in vitro. They effectively restore high level immune responses in a variety of murine models of immunodeficiency both in vivo and in vitro. In this study we examined the potential of these compounds to improve antibody responses generated by cultured cells from patients with common variable immunodeficiency (CVI). The inability to mount normal humoral responses to antigen was confirmed in nine patients with diagnosed CVI (CVI: 37 +/- 16, normal 653 +/- 116 plaque-forming cells (PFC)/culture; P less than 0.001). In cultured lymphocytes from eight of the nine patients studied, a normal level or greater responses to nominal antigen could be elicited by antigen in the presence of the immunostimulatory nucleoside 7-methyl-8-oxoguanosine (7m8oGuo). The average response to antigen increased from 37 +/- 16 without nucleoside to 1733 +/- 488 PFC/culture in its presence (P less than 0.002). Restoration of specific immune responses was an antigen-dependent and nucleoside dose-dependent event. Signaling by 7m8oGuo rendered the response to antigen protein kinase C independent in cultures of cells from normal donors as well as from CVI patients. These data substantiate (i) that a non-C-kinase signaling pathway for antigen-dependent differentiation exists, (ii) that this pathway can function normally in B cells from patients with CVI when triggered appropriately, and (iii) that 7,8-disubstituted guanine ribonucleosides can convert a C-kinase-dependent signaling event to a C-kinase-independent signaling event. Substituted guanine ribonucleosides may have potential as immunotherapeutic agents for patients with CVI.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

In-vivo evaluation of ofloxacin in Salmonella typhimurium infection in mice.

The effects of ofloxacin in Salmonella typhimurium infection in mice were compared with those of ciprofloxacin, ampicillin and chloramphenicol. Oral administration of ofloxacin at 10, 50 or 100 mg/kg once per day for seven days significantly (P less than 0.02) increased survival (20.1 days at 100 mg/kg) of infected mice relative to non-treated controls (4.1 days). In addition, after oral treatment with 100 mg/kg of each of the antibiotics, ofloxacin was significantly more effective than ampicillin (9.9 days), chloramphenicol (8.4 days) or ciprofloxacin (14.9 days) in prolonging the mean survival time of these mice. A comparison of oral potencies indicates that ofloxacin is five times more potent than ciprofloxacin (oral ED50 = 13.3 mg/kg vs ciprofloxacin = 69.9 mg/kg) and over eight times more potent than either of the other two antibiotics. When the number of bacteria from livers and spleens was quantitated, only ofloxacin (25 or 100 mg/kg,po) significantly (P less than 0.02) reduced the number of viable bacteria in both of these tissues in comparison with untreated controls, and, relative to the other antibiotics, ofloxacin (100 mg/kg) caused a significantly greater reduction. Single oral dosing of 20 mg/kg of either ofloxacin or ciprofloxacin showed that ofloxacin achieves approximately a four-fold higher peak serum or liver concentration than ciprofloxacin, which may contribute to its better efficacy in this infection model. These results taken together suggest that oral ofloxacin may be of value in treating systemic salmonella infections in humans.

Ampicillin↗
PubMed1989

Gastric antisecretory and antigastrolesive pharmacology of rioprostil.

Rioprostil, a primary alcohol prostaglandin E1 analogue, inhibits gastric acid secretion, both in vivo and in vitro, and prevents the formation of experimentally-induced gastric lesions in rats and dogs. In vitro experimental evidence suggests that the mechanism of the gastric antisecretory activity of rioprostil involves inhibition of the membrane bound histamine-stimulated adenylate cyclase. In vivo, rioprostil inhibits gastric acid secretion in 4-h pylorus-ligated rats, in gastric fistula dogs stimulated by betazole, tetragastrin, bethanechol, or 2-deoxy-D-glucose, and in Heidenhain pouch dogs stimulated by food. Rioprostil can completely prevent macroscopically visible gastric lesions induced by a variety of noxious agents in rats, including 50% ethanol, aspirin, indomethacin, strong acid, strong base and hypertonic saline. In dogs, rioprostil, but not the H2-blockers cimetidine or ranitidine, totally prevents endoscopically visible gastric lesions induced by aspirin tablets or 60% ethanol, and accelerates the healing of established aspirin-induced gastric lesions from 20 days (vehicle control) to 6 days (33 micrograms/kg p.o., t.i.d.) or 11 days (3 micrograms/kg p.o., t.i.d.). The precise mechanism for the antigastrolesive activity of rioprostil is not known, but may involve increased mucus and bicarbonate secretion, maintaining or increasing gastric mucosal blood flow, increasing the rate of cellular restitution, or possibly antigastrin activity that has been demonstrated in dogs. In rats, rioprostil also prevents duodenal lesions induced by cysteamine, small intestinal lesions induced by indomethacin, and colonic lesions induced by ethanol. The antisecretory and antigastrolesive potency of rioprostil given transdermally to rats is similar to its potency when given systemically, although its diarrhoeagenic potential is lower when given topically compared to oral administration. When used in combination with several non-steroidal anti-inflammatory drugs (NSAIDs) in a model of arthritis in rats, rioprostil inhibits gastric lesion formation without interfering with the anti-inflammatory or analgesic potency of the NSAIDs. In addition, concomitant use of either antacid or cimetidine with rioprostil does not inhibit either the antisecretory or antigastrolesive potency of rioprostil, with the effect of the combination being additive. The doses required to inhibit formation of experimentally-induced gastric lesions in both rat and dog are lower than those required to inhibit gastric acid secretion. This separation of antigastrolesive from antisecretory activity distinguishes rioprostil from other non-prostanoid antisecretory agents, such as histamine H2- receptor antagonists, and establishes rioprostil as a 'selective antigastrolesive agent' (SAGA).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Selective inhibition of 14 alpha-desmethyl sterol synthesis in Candida albicans by terconazole, a new triazole antimycotic.

Terconazole, a new broad spectrum antimycotic triazole derivative, has been shown to have potent activity against Candida albicans in vitro and to be effective in animal models of yeast infections. The present study explored a possible mechanism of anticandidal activity of terconazole. The compound inhibited production of 14 alpha-desmethyl sterols (e.g. ergosterol) in C. albicans at concentrations (IC50 = 3-6 x 10(-9) M) lower than those inhibiting the in-vitro growth of the yeast. There was concomitant accumulation of methylated sterols, (e.g. lanosterol), which are considered detrimental to normal yeast cell membrane function. Terconazole stimulated incorporation of 14C-acetate into triglycerides, but had no other effect on C. albicans lipid metabolism. At concentrations greater than or equal to 10(-6)M terconazole inhibited the oxidation of 14C-acetate into 14CO2 in C. albicans although the mechanism for this effect remains unclear. These data indicate that terconazole is a specific inhibitor of yeast C-14 desmethyl sterol production in C. albicans. Furthermore, terconazole reduced cytochrome P-450 levels in yeast microsomes at concentrations 10,000-fold below those at which it showed effects on rabbit liver microsomes. These data indicate a species specificity for the biochemical actions of terconazole. The C-14 alpha-desmethylase system in yeast cell membranes is cytochrome P-450 associated. Thus, terconazole, was a potent inhibitor of C-14 desmethyl sterol synthesis. This effect could contribute to the anticandidal activity of the drug.

Acetates↗
PubMed1987

Antigastrolesive, gastric antisecretory, diarrheagenic and mucus-stimulating effects in rats following topically applied rioprostil, a synthetic prostaglandin E1 analog.

Prostaglandins may have many biological actions including hypotensive and antipeptic ulcer activity. The purpose of this investigation was to determine if the primary alcohol prostaglandin E1 analog rioprostil1 prevents ethanol-induced gastric lesions (antigastrolesive activity), inhibits gastric acid secretion (antisecretory activity), or causes diarrhea in rats when administered topically, and to compare these responses to the effect of rioprostil following enteral (oral or intraduodenal) administration. Rioprostil exhibited antigastrolesive activity in rats when administered either orally or when applied topically. The topical antigastrolesive potency of rioprostil against ethanol-induced lesions [ED50 = 3.7 (0.5-12) micrograms/kg] was similar to its oral potency [ED50 = 1.9 (1.7-2.2) micrograms/kg]. In 4 hr pylorus-ligated rats, topically administered rioprostil inhibited total gastric acid output with a potency [ED50 = 5.1 (2.6-24) mg/kg] similar to intraduodenal administration [ED50 = 3.7 (2.8-5.3) mg/kg]. In addition, in these rats rioprostil increased mucin levels and did not cause dermal irritation. Finally, the incidence of diarrhea was lower when rioprostil was applied topically than when given orally with a 16-fold difference in potency between these two routes of administration. These data show that when rioprostil is applied via the skin it has antigastrolesive, gastric antisecretory and mucus stimulatory effects in rats equal to enteral administration, and a diarrheagenic potency lower than following oral administration. This profile suggests that topical administration of rioprostil may be a useful means of delivery for clinical treatment of peptic ulcer disease.

Administration, Topical↗
PubMed1987

The antialgesic drugs: human therapeutic correlates of their potency in laboratory animal models of hyperalgesia.

This survey discusses the correlation between the oral potency of antialgesic drugs in several pharmacology laboratories and their human oral dose in clinical practice. We also present a brief overview of a few biological assays that have been successfully used to direct the synthesis of newer antialgesic drugs. The laboratory assay that our analysis showed to be most predictive of the clinical analgesic dose is based upon the response of rats to flexion of an arthritic joint. Laboratory ED50 values from the ACh-induced abdominal constriction assay in mice are nearly as predictive while the predictive power of the yeast-induced hyperalgesia assay in rats is somewhat less. Probably because of the small number of experiments, the correlation between the efficacy of these agents in a canine model of synovitis and their clinical doses only reached borderline statistical significance (p = 0.0651). Regression equations are presented that permit calculations of single clinical analgesic doses from efficacy data in individual tests. Calculation of stepwise multiple regression showed that the clinical dose could be best predicted when efficacy data obtained in the joint flexion assay in rats and the ACh-induced constriction assay in mice are both taken into account. We have concluded that the effective doses are highly predictive of clinical efficacy because these animal assays have been designed to reflect the action of drugs upon prostanoid-induced hyperalgesia.

Acetylcholine↗
PubMed1987

Selective gastric antilesion properties of rioprostil, a prostaglandin E1 analog, in rats and dogs.

This paper characterizes the ability of rioprostil, a synthetic primary alcohol prostaglandin E1 analog, to inhibit gastric acid secretion and prevent experimentally induced gastric lesions in rats and dogs, and determines the selectivity (the separation in potency) for these effects. In 4-hr pylorus ligated rats, rioprostil inhibited gastric acid output when administered i.v., s.c., p.o. or intraduodenally, with ED50 values of 0.9, 1.8, 2.9 and 3.7 mg/kg, respectively. Rioprostil suppressed meal-stimulated acid output in Heidenhain pouch dogs and inhibited gastric acid output stimulated by tetragastrin, 2-deoxy-D-glucose, betazole or bethanechol in gastric fistula dogs with ED50 values of 7, 10, 16 and 17 micrograms/kg p.o., respectively. These values in dogs were not significantly different from each other, suggesting that the mechanism of the antisecretory effect of rioprostil is similar regardless of the secretagogue used. Rioprostil prevented ethanol induced gastric lesions in rats (ED50 = 1.5 micrograms/kg p.o.; 12.0 micrograms/kg s.c.) after a 30-min pretreatment. The 8-fold difference in potency between the p.o. and s.c. routes may reflect a local component in the antilesion mechanism of rioprostil. In dogs, rioprostil inhibited aspirin-induced gastric lesions with a p.o. ED50 of 1.6 micrograms/kg. Maximum antilesion activity in dogs for cimetidine or ranitidine was less than 50%, whereas rioprostil inhibited lesion formation by 100% without the appearance of side effects. Oral antilesion selectivity of rioprostil in rats (antisecretory ED50/antilesion ED50) was nearly 2000-fold using the optimum pretreatment time (30 min), and was 12-fold when the pretreatment time (4 hr) was the same as the duration of the antisecretory assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Anticandidal activities of terconazole, a broad-spectrum antimycotic.

Terconazole is a new triazole ketal derivative with broad-spectrum in vitro and in vivo antifungal activities. This study further characterizes the effects of terconazole in vitro on yeast cell growth, viability, and morphology. Terconazole inhibited the growth of Candida albicans ATCC 44859 in a concentration-related manner, but with modest effects noted at levels from 10(-8) to 10(-5) M when the yeast was grown on media favoring the cell form. The inhibitory potency of terconazole on yeast cell viability varied with the strain and species of Candida tested. The susceptibility of C. albicans ATCC 44859 to terconazole was markedly enhanced when the yeast was grown on Eagle minimum essential medium, which favors mycelium formation. The effects of terconazole on the morphology of yeast cells (grown on Eagle minimum essential medium) were shown by phase-contrast and electron microscopy. There is a progression of changes, from loss of mycelia formation at 10(-8) M terconazole through complete necrosis at 10(-4) M.

Antifungal Agents↗
PubMed1985

Potent and selective effects of suprofen on uterine prostaglandin synthesis.

Suprofen is a non-narcotic, peripheral analgesic that exhibits potent prostaglandin (PG) synthesis inhibitory activities in a variety of subcellular tissue preparations and in vivo. The results of the present study show suprofen to be significantly more potent than either ibuprofen (6-fold) or aspirin (1000-fold) as an inhibitor of PG production by cell-free preparations of guinea pig uteri. It is selectively more potent against the production of PGF2 alpha and PGE2 than against the formation of 6-keto PGF1 alpha, the stable metabolite of prostacyclin. Suprofen is markedly more potent inhibiting the conversion of arachidonic acid to PGF2 alpha than is ibuprofen (30 times) or aspirin (1250 times). Taken together with the important role PGF2 alpha plays in the etiology of dysmenorrhea and the observation (Hahn et al., 1982) that suprofen is more potent and effective than a number of other PG synthesis inhibitors, including ibuprofen and aspirin, at reducing in vivo guinea pig uterine contractions induced by arachidonic acid, the results of the present study suggest a mechanism to support the clinical findings that suprofen is a very effective treatment for the signs and symptoms of dysmenorrhea.

Animals↗
PubMed1985

Pharmacology of rioprostil, a new gastric cytoprotective/antisecretory agent.

Rioprostil (2-decarboxy-2-hydroxymethyl-15-deoxy-16RS-hydroxy-16-methyl prostaglandin (PG)E1) is a potent orally active inhibitor of gastric acid secretion in both rats and dogs. It prevents gastric lesions in rats induced by ethanol, acetylsalicylic acid, strong acid, strong base, hypertonic saline and thermal injury at doses 100 times less than its antisecretory dose. The cytoprotective effect of rioprostil can be observed when given 4 min before challenge with ethanol and measured 60 min later. The peak antiulcer effect is observed when rioprostil is given 30 min before ethanol challenge and the oral ED50 is 1.93 (1.74-2.15) micrograms/kg. Rioprostil possesses weak PGE-like activity in an isolated tissue cascade, no contragestational activity in rats, hamsters or rabbits, and no remarkable cardiovascular or pulmonary activity in dogs. The animal pharmacology of this compound suggests that it should be useful in the treatment or prophylaxis of peptic ulcer disease and gastric lesions associated with noxious irritants such as ethanol and nonsteroidal antiinflammatory drugs.

Animals↗
PubMed1984

Antifertility activity and general pharmacological properties of ORF 13811: a synthetic analog of zoapatanol.

ORF 13811, a synthetic analog of zoapatanol, was evaluated in a variety of in vivo and in vitro biological test systems to determine antifertility and uterotonic activity as well as its general pharmacological profile. ORF 13811 is a potent antifertility agent after oral administration in a number of animal species including mice, rats, guinea pigs, dogs and baboons. The single oral ED50 for contragestational activity in the pregnant guinea pig (day 22), mouse (day 16) and rat (day 16) is in the range of 6 to 10 mg/kg. In pregnant beagle dogs, a dose-related contragestational effect was obtained within several days after oral administration of ORF 13811 in the dosage range of 10 to 30 mg/kg. ORF 13811, when administered to pregnant baboons, caused dose-related vaginal bleeding and evacuation of uterine contents within 3 days following treatment with oral doses of 40 to 60 mg/kg. Serum progesterone levels were decreased in baboons and the degree of reduction correlated with contragestational activity. ORF 13811 was also effective in inhibiting implantation in mice, rats and hamsters, but required higher dose levels than those of the post-implantive treatments. In vitro uterotonic properties of ORF 13811 were demonstrated by its ability to induce contraction of uterine strips obtained from female guinea pigs at two different reproductive stages (day 15 of the estrous cycle and day 22 of pregnancy). In these preparations ORF 13811 was approximately 1/30 to 1/50th as potent as PGF2 alpha. In a series of pharmacological tests, ORF 13811 was found to possess slight sedative properties but was devoid of activity on pulmonary, gastrointestinal, and immune systems as well as in a number of biochemical tests, data not reported here. However, in cardiovascular studies, ORF 13811 appears to possess a vasoconstrictor profile in the dog, monkey and baboon as indicated by an increase in mean arterial blood pressure as well as total peripheral and regional vascular resistances. The in vitro pharmacological profile of ORF 13811 was examined in myocardial tissue and vascular smooth muscle test systems and compared to PGF2 alpha. ORF 13811 was found to contract rat aortic strips, 15 times less potent than PGF2 alpha. The compound had no direct effect on isolated guinea pig atria or papillary muscle. In summary, ORF 13811 is a potent orally active antifertility agent characterized primarily as a contractor of uterine and vascular smooth muscle.

Animals↗
PubMed1984

The comparative bronchodilator properties of alkyl quaternary salts of promethazine.

Several salts of thiazinamium, a quaternary analogue of promethazine, administered by aerosol, possessed equipotent anticholinergic activity in anesthetized guinea pigs but the duration of this effect differed somewhat. N-Butyl substitution in the side chain, but not the corresponding ethyl or n-propyl substitutions, reduced the aerosol anticholinergic potency and duration. There was also a tendency for a corresponding reduction in antihistaminic activity with different alkyl substitutions and for a greatly reduced duration of this effect.

Aerosols↗
PubMed1984

Suprofen: the pharmacology and clinical efficacy of a new non-narcotic peripheral analgesic.

Suprofen is a potent, peripherally-acting, non-narcotic analgesic agent. The mechanism of action of the compound involves inhibition of prostaglandin biosynthesis and, perhaps, direct antagonism of the peripheral, pain inducing actions of prostaglandins, bradykinin and other pain mediators. Suprofen at a dose of 200 mg appears to be equal or greater in efficacy as an analgesic modality than those of ibuprofen, propoxyphene, naproxen and diflunisal or a combination of 650 mg aspirin plus 60 mg codeine. Its clinical utility has been amply demonstrated in the treatment of a number of types of pain including general and orthopedic surgery, episiotomy, post-partum pain, dysmenorrhea, dental pain and musculoskeletal disorders. Suprofen represents a new class of orally effective nonnarcotic analgesics with potential for effective clinical use in the treatment of pain.

Animals↗
PubMed1983

Tissue selectivity and variability of effects of acetaminophen on arachidonic acid metabolism.

Acetaminophen has variable effects on prostaglandin synthesis depending on the tissue preparation used. The present study was designed to determine the effects of acetaminophen on arachidonic acid metabolism in different tissues simultaneously removed from the same animals treated with the compound. The ex vivo conversion of 14C-arachidonic acid into 14C-prostaglandins was monitored in homogenates or slices of tissues to which no exogenous cofactors were supplied. Administered orally at doses of 100-300 mg/kg to guinea pigs, acetaminophen stimulated prostaglandin production by cell-free preparations of stomach, but had no effect in lung or kidney medulla. At doses ranging from 25-300 mg/kg, p.o., to rats, acetaminophen stimulated stomach, but inhibited cerebral cortex prostaglandin production. These same effects were mimicked qualitatively when acetaminophen was added in vitro at 10(-4)M to 10(-2)M to similar preparations. In addition, at these same high concentrations, acetaminophen inhibited 5-lipoxygenase activity in cultured RBL-1 cells. It is speculated that the multiple and tissue variable effects that acetaminophen had on arachidonic acid metabolism depend on the inherent cofactors associated with each tissue type.

Acetaminophen↗