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PubMed1995

Effects of iodinated contrast media on pulmonary airway resistance in anesthetized guinea pigs.

RATIONALE AND OBJECTIVES: Bronchospasm is occasionally observed following iodinated X-ray contrast medium administration. We performed an in vivo study in guinea pigs to investigate the effects of a number of iodinated contrast media on pulmonary airway resistance and the mechanisms underlying the potential bronchoconstrictor effect. METHODS: The contrast media studied were the pharmaceutical formulations of iomeprol (400 mg I/ml), iopamidol (370 mg I/ml), and iohexol (350 mg I/ml), which are nonionic, triiodinated contrast media; diatrizoate (370 mg I/ml), an ionic, triiodinated contrast medium; iotrolan (300 mg I/ml), a nonionic, hexaiodinated contrast medium; and iocarmate (280 mg I/ml) and ioxaglate (320 mg I/ml), which are both hexaiodinated and ionic contrast media. Each contrast medium was administered intravenously at 2 g I/kg. Changes in pulmonary airway resistance were evaluated by measuring intratracheal pressure at the moment of maximum insufflation, or maximal insufflation pressure (MIP), in anesthetized guinea pigs submitted to forced ventilation. RESULTS: All contrast media except ioxaglate caused mean increases of MIP of no more than 20%. By contrast, ioxaglate caused a marked bronchoconstrictor effect, increasing MIP by 242% +/- 46%. Of the drugs tested for antagonistic action on this increase in MIP, salbutamol inhibited almost completely the increase in MIP for the first 40 min posttreatment. Similarly, lysine acetylsalicylate and indomethacin consistently reduced MIP after contrast media administration to levels only 30% and 14% above those of baseline precontrast media, respectively. Promethazine had only a minor inhibitory effect, and the response to prednisolone varied. CONCLUSION: There was no apparent relationship between the size of the increase in airway resistance and the charge or molecular weight of the contrast agent molecule or the pharmaceutical formulation. The increase induced by ioxaglate must be attributed to inherent molecular toxicity mediated through a direct action on the production of bradykinin and/or the prostanoid products of the cyclooxygenase pathway, rather than through a direct action on the release of histamine.

Airway Resistance↗
PubMed1981

Side-chain effects on phenothiazine cation radical reactions.

The cation radical of each of the phenothiazine tranquilizers is a likely intermediate in the metabolism of the drugs to at least two of the three major metabolic classes, the sulfoxides and the hydroxylated derivatives. Previous work has shown that the reactions of the radical are highly dependent on the environment, particularly the presence of nucleophiles. The present report discusses the effect of cation radical structure on the formation of sulfoxide and hydroxylated metabolites in vitro. Cyclic voltammetry, spectrophotometry, and liquid chromatography were used to examine reactions of various phenothiazine radicals in aqueous buffers. A radical with a three-carbon aliphatic side chain (e.g., chlorpromazine) forms solely sulfoxide and parent unless amine nucleophiles are present, in which case hydroxylation occurs. A shorter side chain (e.g., promethazine) causes radical dimerization and pronounced hydroxylation, regardless of external nucleophiles. A piperazine side chain (e.g., fluphenazine) promotes hydroxylation, with some sulfoxide observed. The results indicate that a deprotonated amine is necessary for hydroxylation and that the amine may be present in the original drug rather than an external nucleophile. In addition to information about cation radical reactions, the redox properties of several different phenothiazines are presented.

Cations↗
PubMed1985

New antihistaminic theophylline or theobromine derivatives.

A series of 3,4-dihydro-1,3-dimethyl-7-[3-(4-substituted-piperazin-1-yl)- substituted-alkyl]-1H-purine-2,6-diones and 3,7-dihydro-3,7-dimethyl-1-[3-(4-substituted-piperazin-1-yl)- substituted-alkyl]-1H-purine-2,6-diones was synthesized and evaluated for antihistaminic activity. Some of them displayed good inhibition of both histamine-induced bronchospasm in the anesthetized guinea pig at 10 micrograms/kg by the intravenous route and of passive cutaneous anaphylaxis in the rat at 10 mg/kg by the oral route. Comparison of the two most active compounds revealed a higher antihistaminic activity with the compounds containing a (phenylthio)propyl group (1 and 2) as compared with that containing a phenoxy group. Compound 2 [RS-49014, 3,4-dihydro-1,3-dimethyl-7-[3-[4-[3-(phenylthio)propyl]piperazin-1 -yl]- 2-hydroxypropyl]-1H-purine-2,6-dione] was selected for clinical trials on the basis of a comparative pharmacological study with chlorpheniramine, ketotifen, promethazine, and theophylline.

Acetylcholine↗
PubMed1992

Reversal of signs of induced cotton effects of dicumarol-alpha 1-acid glycoprotein systems by phenothiazine neuroleptics through ternary complexation.

The interaction of dicumarol and phenothiazine neuroleptics binding to alpha 1-acid glycoprotein (AGP) was investigated by circular dichroism (CD) and equilibrium dialysis. The induced CD spectra of the dicumarol-AGP complex were affected differently by the different substituents of the phenothiazine molecule. The sign of the induced Cotton effect of dicumarol bound to AGP was reversibly changed with the introduction of the propyldimethylamine substituent at position 10 or chloride group at position 2 of the phenothiazine molecule. Chlorpromazine, which contains both of these substituents reversed the sign of the induced Cotton effect with the highest intensity. The addition of trifluoperazine, fluphenazine, and promethazine containing neither of the two substituents generated a new negative CD band. However, the addition of opromazine, which contains sulfoxide at position 5, decreased the CD intensity of the dicumarol-AGP complex without changing the shape of the CD spectra. Equilibrium dialysis studies revealed that the interaction of dicumarol-AGP with phenothiazine derivatives occurred simultaneously, and the interaction followed a cooperative and anticooperative binding model. Further, among the six phenothiazine derivatives that reversed the signs of the induced Cotton effects of the dicumarol-AGP complex, a linear relationship was observed between coupling constants and the difference in the induced optical ellipticity. The opromazine and dicumarol interaction was competitive for a common binding site on the AGP molecule. Removal of sialic acid did not have any effect on this interaction. These data support the hypothesis that the acidic and the basic drug binding sites overlap each other.

Antipsychotic Agents↗
PubMed1998

Paraquat-induced cell death in PC12 cells.

Paraquat was taken up by PC12 cells in a carrier-mediated, saturable manner. When PC12 cells were permeabilized with digitonin (50 microg/ml) lipid peroxidation was observed after paraquat treatment in the presence of NADPH and chelated iron. The fact that lipid peroxidation preceded the appearance of LDH release provides positive evidence that lipid peroxidation may be one of the important factors leading to cytotoxicity of cells. Furthermore, the fact that addition of superoxide dismutase, catalase and promethazine efficiently blocked the malondialdehyde formation and attenuated the cell death indicated the involvement of reactive oxygen radicals in mediating the cytotoxicity induced by paraquat. Taken together the results present in vitro evidence that neurotoxicity of paraquat may be a consequence of cellular lipid peroxidation, which leads to cell death and may have great implications in assessing the risk of exposure to paraquat in Parkinson's disease.

Animals↗
PubMed2003

Effect of phenothiazines on protein kinase C- and calcium-dependent activation of peritoneal macrophages.

The effects of some phenothiazines (promethazine, PMZ; chlorpromazine, CPZ; levomepromazine, LVPZ; thioridazine, TRDZ; trifluoperazine, TFPZ) on the activation and viability of rat peritoneal macrophages were investigated. The macrophage activation was estimated by measuring of luminol-dependent chemiluminescence, induced by phorbol-12-myristate-13-acetate (PMA) (a protein kinase C activator) or calcium ionophore A23187. The viability of macrophages was determined using ATP bioluminescence as a criterion of cell viability. It was observed that all drugs, in concentrations higher than 1 micromol/L, markedly decreased the chemiluminescent index of PMA-activated or A23187-activated macrophages. The inhibitory effect was dose-dependent. It was better expressed in the case of CPZ, followed by TFPZ and TRDZ, and less expressed in the case of PMZ and LVPZ. The suppression of chemiluminescence of PMA-/A23187-activated macrophages by phenothiazines was not a result of their cytotoxic effect. Moreover, it was found that all drugs dose-dependently enhanced the viability of macrophages, estimated by ATP production. The inhibitory effects of phenothiazines on the chemiluminescence of PMA-/A23187-activated macrophages were greater than their ability to decrease KO2-induced chemiluminescence as a result of interaction with superoxide radicals. It may be supposed that the inhibitory effect of phenothiazines on PMA-/A23187-induced chemiluminescence of macrophages is a result not only of interaction between drugs and superoxide radicals, generated during the "oxidative burst" of activated cells. Presumably the drugs have an immunomodulating effect on rat peritoneal macrophages.

Adjuvants, Immunologic↗
PubMed2003

Solubilization of cationic drugs in lung surfactant.

PURPOSE: The association of hydrophobic, cationic drugs with lung surfactant was determined to assess the pharmacokinetic implications on drug disposition and retention in the lung. METHODS: The distribution coefficients, K, were determined at 25 and 37 degrees in normal saline solution buffered at pH 7.4 for a series of structurally related, cationic drugs. Drugs were dispersed into lung surfactant, equilibrated, and then centrifuged to separate the aqueous phase from the surfactant pellet. Drug concentrations in the supernatant and pellet were determined following dilution using spectrophotometric assays. In addition, the apparent acid dissociation constant of quinacrine in the presence and absence of surfactant was determined by measuring the pH-dependent absorption spectra. The effect of stereochemistry on the distribution of drugs into surfactant was examined with (R)- and (S)-propranolol. RESULTS: The mole fraction distribution coefficients for amitriptyline, promethazine, promazine, ethopropazine, imipramine, R-propranolol, and S-propranolol at 25 degrees C were 6,560 +/- 500, 28,400 +/- 1,500, 12,100 +/- 840, 5,480 +/- 330, 4,490 +/- 250, 8,680 +/- 260, 8,190 +/- 530, respectively. At 37 degrees C, the distribution coefficients were generally smaller indicating a significant exothermic heat of transfer for these solutes from aqueous solution to the lung surfactant. The pKa of quinacrine was 7.43 +/- 0.04 in aqueous solution and was shifted to 7.62 +/- 0.06 in the presence of lung surfactant. From this shift, the double layer potential for quinacrine-lung surfactant was estimated to be -0.012 V assuming a dielectric constant equivalent to that of water. CONCLUSIONS: Cationic drugs have very favorable distributions from an aqueous solution to the lipid phase of lung surfactant. The transfer process generally has both a large entropic and enthalpic contribution. The latter thermodynamic aspect may be related to the charge interaction between the solute and the negatively charged surfactant. Finally, no significant effect of stereochemistry was evident with the distribution of (R)- and (S)-propranolol.

Cations↗
PubMed2003

Inactivation of cholinesterase induced by chlorpromazine cation radicals.

To clarify the mechanism of the side effect of chlorpromazine, we examined the inactivation of cholinesterase induced by chlorpromazine. Cholinesterase was inactivated and its activity was lost in rat serum during interaction of chlorpromazine with horseradish peroxidase and H2O2. When chlorpromazine was oxidized by horseradish peroxidase and H2O2, the reaction solution colored pink and the visible absorption spectrum was consistent with the absorption spectrum of the chlorpromazine cation radical (CPZ*+). Adding cholinesterase immediately decreased the pink color of CPZ*+, indicating that CPZ*+ directly attacked cholinesterase to cause loss of the enzyme activity. Tryptophan residues in cholinesterase sharply decreased during the interaction of cholinesterase with horseradish peroxidase and H2O2. Presumably, loss of tryptophan residues changed the conformation of the cholinesterase protein and then the activity of the enzyme was lost. Other phenothiazine derivatives, including promethazine, triflupromazine, trifluoperazine, trimeprazine, thioridazine and perphenazine, also inactivated cholinesterase during the oxidation by horseradish peroxidase and H2O2. These results suggest that phenothiazine cation radicals participate in toxicological signs caused by the drugs.

Animals↗
PubMed1991

No causal relationship between transdermal scopolamine and seizures: methodologic lessons for pharmacoepidemiology.

Because of case reports suggesting that use of transdermal scopolamine might be associated with the subsequent development of seizures, a retrospective cohort study was performed with computerized Medicaid claims data. Patients receiving transdermal scopolamine were compared with patients receiving diphenhydramine, meclizine, prochlorperazine, and promethazine. A four-fold increased risk of seizures after transdermal scopolamine use was observed in the claims data. However, this was not supported by the primary medical records. All patients who had seizures after using transdermal scopolamine either had seizures before receiving the drug as well or did not really suffer from seizures. The original finding appeared to be the result of the use of transdermal scopolamine for "dizziness, rule out seizures"; the ICD-9-CM coding system does not include "rule out" diagnoses. Thus these data do not confirm the existence of an association between seizures and the use of transdermal scopolamine. In addition, this study demonstrates the usefulness of pharmacoepidemiology studies in documenting drug safety and the importance of obtaining primary medical records when performing pharmacoepidemiologic studies with claims data.

Administration, Cutaneous↗
PubMed1979

Effects of carbon tetrachloride on isolated rat hepatocytes. Inhibition of protein and lipoprotein secretion.

The effects of carbon tetrachloride on protein and lipoprotein secretion, and on lipid peroxidation, have been investigated in isolated rat hepatocytes. It was found that although the free-radical scavenger promethazine completely suppressed the increased peroxidation produced by carbon tetrachloride, it had no effect on the inhibitory action of carbon tetrachloride on lipoprotein secretion. In consequence, the latter effect of carbon tetrachloride does not appear to be mediated through a peroxidative stage.

Animals↗
PubMed1980

Stimulation of peripheral dopamine receptors in rats: a mechanism for novel antihypertensive agents.

1. The aim of this investigation was to provide support for the hypothesis that stimulation of peripheral dopamine receptors reduces sympathetic vasomotor tone and thus may be a mechanism for novel antihypertensive agents. 2. NN-Di-n-propyldopamine (DPDA: 0.03-0.1 mg min-1 kg-1 intra-arterially) produced sustained decreases in blood pressure measured from the cannulated tail artery in conscious spontaneously hypertensive rats. 3. This antihypertensive action of DPDA was antagonized by sulpiride but not by atropine, promethazine, propranolol or indomethacin. 4. DPDA failed to lower blood pressure in spontaneously hypertensive rats in which peripheral stores of catecholamines had been previously depleted with syrosingopine. 5. In the pithed atropine-pretreated spontaneously hypertensive rats in which the low blood pressure was elevated by electrical stimulation of the spinal cord, DPDA produced hypotensive effects which were antagonized by sulpiride. However, DPDA, in contrast to phentolamine, did not modify the blood pressure raised by an infusion of adrenaline. 6. In conclusion, the blood pressure-lowering action of DPDA is due to stimulation of dopamine receptors which decreases noradrenaline release and consequently sympathetic vasomotor tone. These receptors may be located on sympathetic ganglia or sympathetic endings innervating resistance vessels.

Animals↗
PubMed2000

Safety and efficacy of transurethral resection of the prostate under sedoanalgesia.

OBJECTIVE: To assess the safety and efficacy of sedoanalgesia (local anaesthesia with sedation) in patients with benign prostatic hyperplasia (BPH) undergoing transurethral resection of the prostate (TURP). PATIENTS AND METHODS: The study comprised 50 patients with BPH, two-thirds of whom were graded III-IV using the American Society of Anesthesiologists system. All patients had a topical instillation of lignocaine jelly 2% into their urethra, combined with 1% lignocaine (100-200 mg) with 1 : 400 000 adrenaline infiltration of the prostate via the perineal route. Sedation and anxiolysis were obtained with the intramuscular pethidine (0.5 mg/kg) and promethazine (1 mg/kg). Standard TURP was then carried out, with pain monitored during surgery using a visual analogue scale (VAS, maximum 10 points) and the amount of analgesic required after TURP recorded. The amount of prostatic tissue excised, duration of surgery, blood requirement, catheter interval, complications and hospital stay were recorded. The effectiveness of TURP was assessed by comparing symptom scores, uroflowmetry and postvoid residual volume before and after surgery. RESULTS: The mean intraoperative VAS was < or = 1 at any time during or after surgery; no patient required any postoperative analgesics. Only two patients complained of discomfort during the procedure and even they were comfortable after a supplemental dose of pethidine (12.5 mg). There were no conversions to general or regional anaesthesia. No blood transfusion was required in any patient. All patients began a normal diet 30 min after surgery and all were discharged within 48 h of surgery. There were no deaths; one patient had transient urinary incontinence and three had mild urinary tract infection. CONCLUSION: Sedoanalgesia was an effective, safe and simple alternative to general or regional anaesthesia for TURP in patients with BPH.

Adult↗
PubMed1997

Beta-amyloid neurotoxicity in vitro: evidence of oxidative stress but not protection by antioxidants.

Recent data from several groups suggest that the primary mechanism of beta-amyloid neurotoxicity may be mediated by reactive oxygen species. To evaluate this hypothesis, we first compared the efficacy of antioxidant agents in preventing toxicity caused by oxidative insults (iron, hydrogen peroxide, and tert-butyl hydroperoxide) and beta-amyloid peptides in cultured rat hippocampal neurons. Tested antioxidants (propyl gallate, Trolox, probucol, and promethazine) generally provided significant protection against oxidative insults but not beta-amyloid peptides. Next, we examined whether beta-amyloid causes oxidative stress, by comparing levels of lipid peroxidation after exposure to either iron or beta-amyloid. In a cell-free system, iron but not beta-amyloid generated lipid peroxidation. In culture, both insults caused rapid increases in lipid peroxidation, with iron inducing higher levels at later time points. Pretreatment with the antioxidant probucol significantly reduced lipid peroxidation caused by both insults but only attenuated iron toxicity, suggesting that lipid peroxidation does not contribute directly to cell death induced by beta-amyloid. Finally, we observed that increasing basal levels of oxidative stress by pretreating cultures with subtoxic doses of iron significantly increased neuronal vulnerability to beta-amyloid. The ability of beta-amyloid to induce oxidative stress and the demonstration that oxidative stress potentiates beta-amyloid toxicity support the clinical use of antioxidants for AD. However, these data do not support the theory that the primary mechanism of beta-amyloid toxicity involves oxidative pathways, indicating a continued need to identify additional cellular responses to beta-amyloid that underlie its neurodegenerative actions.

Amyloid beta-Peptides↗
PubMed1998

Acute treatment of periodic severe headache: comparison of three outpatient care facilities.

We compared treatment of patients with episodic, severe, migraine-vascular headaches in three outpatient settings associated with a major medical center: the Charlton Outpatient Therapy Center (COTC), a dedicated transfusion and injection facility which provides treatment based on physician orders written in advance of the patient's visit; a walk-in Urgent Care Center (UCC); and a traditional hospital emergency trauma unit (ETU). For a 7-month period in 1995, all patient visits for acute migraine headache to the COTC, UCC, and ETU were reviewed. Data collected included the treatment and charges. After the study period, a sample of patients was surveyed regarding their outcome and satisfaction with care at each of the three facilities. During the study period, 15 patients visited the COTC 446 times for the treatment of acute migraine, 80 patients visited the UCC 233 times, and 182 patients visited the ETU 238 times. The average charges per visit were $39.93 for the COTC, $57.28 for the UCC, and $317.71 for the ETU. Average time spent in order to obtain care was 35 minutes in the COTC, 62 minutes in the UCC, and 105 minutes in the ETU. Intramuscular meperidine with either promethazine or hydroxyzine was the most commonly administered treatment in all three settings. Patients treated in the COTC reported greater satisfaction than the patients seen in the UCC or ETU. A dedicated outpatient facility with extended hours of operation and the capability of treating acute headache patients with parenteral medications based on standing orders has provided a community of migraine sufferers with cost-effective care.

Acute Disease↗
PubMed2003

Feasibility of amifostine administration in conjunction with high-dose rate brachytherapy.

This ongoing study was initiated to determine the feasibility of administering amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD) with monomodal high-dose rate (mHDR) brachytherapy and to assess the tolerability and side effects of this combination. To date, 18 patients suitable for prostate implant brachytherapy (<or=T2aN0; prostate-specific antigen <or= 10 ng/mL; Gleason score <or= 6) have been treated with mHDR brachytherapy, receiving four 9-Gy fractions administered twice daily for 2 days. Amifostine (500 mg) is administered subcutaneously on the day before implant and 30 to 60 minutes before the first and third mHDR treatments. All 18 patients have received amifostine and brachytherapy as planned. Nausea was manageable with oral prochlorperazine in the pretreatment phase and our standard antiemesis protocol (intravenous promethazine, with granisetron if needed) during the implant; hypotension and asthenia were not problematic. During the 2-week post-treatment phase, grade 1 cystitis occurred in eight of 18 patients; grades 1 and 2 proctitis occurred in six of 18 and five of 18 patients, respectively. Six patients developed urinary obstruction symptoms. Preliminary results support the feasibility and tolerability of subcutaneous amifostine in conjunction with mHDR brachytherapy. Total accrual goal is 50 patients to assess long-term efficacy. Additional studies of HDR with amifostine are planned for patients with recurrent prostate and gynecologic cancer.

Amifostine↗
PubMed2002

A systematic approach to the management of postoperative nausea and vomiting.

Postoperative nausea and vomiting (PONV), a common complication after anesthesia and surgery, often results in delayed discharge with the patient's unpleasant symptoms continuing at home. To effectively prevent and treat PONV, it is important to understand the factors implicated in PONV, the mechanisms of PONV, the pharmacology of the antiemetic agents, and the nonpharmacologic measures that have been shown to be effective. The cause of PONV is likely to be multifactorial, with important predictors being female gender, history of PONV, and history of motion sickness. The vomiting center can be triggered by activation of dopamine, serotonin (type 3), histamine (type 1), and muscarinic cholingergic receptors in the chemoreceptor trigger zone and the nucleus tractus solitarus, as well as acetylcholine receptors in the vestibular apparatus, vagal afferents from the periphery, and the endocrine environment. Antiemetic agents such as the serotonin antagonists (eg, ondansetron, dolasetron), droperidol, antihistamines (eg, diphenhydramine, dimenhydrinate), and promethazine can prevent and treat PONV effectively. Transdermal scopolamine and dexamethasone have a role in the prevention of PONV, particularly for certain high-risk patients. Nonpharmacologic measures and alternative treatments such as hydration, maintaining blood pressure, acupressure techniques, trancutaneous acupoint stimulation, and isopropyl alcohol must not be overlooked. Finally, an evidence-based algorithm for the prevention and treatment of PONV in adults is presented.

Algorithms↗
PubMed2000

Human term placental lipoxygenase-mediated N-demethylation of phenothiazines and insecticides in the presence of linoleic acid.

This study investigated the hypothesis that human term placental lipoxygenase (HTPLO) and soybean lipoxygenase (SLO) are capable of mediating N-demethylation of selected phenothiazines and insecticides in the presence of linoleic acid (LA). In addition to being LA dependent, the N-demethylation reaction mediated by HTPLO and SLO was limited by incubation time, pH of the medium, concentration of the enzyme and the substrate. Using Nash reagent to monitor formaldehyde production, the specific activity for LA-dependent N-demethylation of chlorpromazine, a model phenothiazine, was determined to be 1.7+/-0.3 nmoles/min/mg HTPLO. Besides chlorpromazine, N-demethylation of promazine, promethazine and trimeprazine was also observed. The insecticide, aminocarb, displayed a specific activity of 2.2+/-0.3 nmoles/min/mg HTPLO for N-demethylation. Other insecticides, namely chlordimeform, dicrotophos and zectran, were oxidized in a similar manner. As compared with HTPLO, the rates of N-demethylation of phenothiazines and insecticides mediated by SLO were higher. Classical inhibitors of lipoxygenase, as well as antioxidants and free radical scavengers, caused a dose-dependent reduction in the production of formaldehyde from chlorpromazine and aminocarb by HTPLO. These results clearly demonstrate the ability of polyunsaturated free fatty acids to support N-demethylation of xenobiotics via the lipoxygenase pathway.

Carbamates↗
PubMed1995

Antioxidant activity of fruit exudate and C-methylated dihydrochalcones from Myrica gale.

Antioxidant and radical scavenging effects were studied of a diethyl ether extract of the fruit exudate of Myrica gale L., and of C-methylated dihydrochalcones isolated from it. Isolated hepatocytes and liver mitochondria from the rat were incubated with tertbutyl hydroperoxide, and lipid peroxidation measured by the yield of thiobarbituric acid reactive substances. The main antioxidant of the extract, myrigalone B (MyB), inhibited lipid peroxidation in hepatocytes with an IC50 value of 23 +/- 1 microM, whereas in mitochondria the value was 5.2 +/- 0.1 microM. The fruit extract itself inhibited peroxidation in hepatocytes with an IC50 value of 7.0 +/- 0.2 microM calculated according to its MyB content, and in mitochondria with an IC50 of 1.7 +/- 0.1 microM. Other myrigalones were considerably less active or inactive as antioxidants. The IC50 of promethazine, an established inhibitor of lipid peroxidation, was 3.8 +/- 0.4 microM in mitochondria./ Both MyB and the fruit extract caused scavenging of the diphenylpicrylhydrazyl (DPPH) radical with IC50 values of 32 +/- 1 microM and 14 +/- 1 microM (as MyB), respectively. Peroxidation in linoleic acid catalyzed by soybean 15-lipoxygenase was inhibited by MyB (IC50 = 23 +/- 1 microM calculated as MyB; corresponding to an extract concentration of 71 +/- 3 microgram(s)/ml). However, the extract content of myrigalone A, itself a fairly potent inhibitor of 15-lipoxygenase, may contribute significantly to the latter effect.

Animals↗