Aflatoxin deposition and clearance in the eggs of laying hens

Hens fed a diet containing 3310 μg of AFB₁ and 1680 μg of AFB₂ per kg feed for 28 days showed a significant decrease in egg production and egg weights by wk 3 and 4 of feeding, respectively. Transfer of aflatoxins to the eggs occurred rapidly, reaching maximum levels after 4–5 days, and remained relatively constant throughout aflatoxin feeding. The mean values for combined residue levels in eggs were less than 0.5 μg/kg. Levels of AFB₂, AFM₁ and AFM₂ were similar in yolk and albumen while levels of B₁ and B_2a were higher in the yolk. Upon removal of the aflatoxin-containing diet, residues in eggs decreased rapidly. Clearance of aflatoxin residues from the albumen occurred faster than from the yolk. Thus, no residues were detected in the albumen and in the yolk after 5 and 7 days of withdrawal, respectively. No aflatoxin residues could be recovered from whole eggs after feeding the aflatoxin-free diet for 4 days.     

Activity of some respiratory enzymes and cytochrome contents in rat hepatic mitochondria following aflatoxin B1 administration

Effects of aflatoxin B₁ (AFB₁) administration (7 mg/kg body weight i.p.) on rat hepatic mitochondrial respiratory components have been examined. Succinoxidase and cytochrome oxidase activities were decreased in liver mitochondria isolated from rats 12–24 h after AFB₁ treatment. Both enzyme activities returned to normal levels after 48 h. Glutamate dehydrogenase and β-hydroxybutyrate dehydrogenase activities did not show any alterations up to 24 h and thereafter increased at 48–72 h. Succinate dehydrogenase activity was impaired by 41% at 12 h and thereafter was found to be normal. The intramitochondrial cytochrome b content declined at 24–72 h, whereas cytochrome aa₃ content was decreased maximally at 72 h after AFB₁ administration. These observations on mitochondrial enzyme activities and cytochrome contents correlate well with our earlier observations made on hepatic mitochondrial respiratory rates after AFB₁ treatment. The impairment of respiratory functions possibly results from membrane damage and selective modification of gene expression in mitochondria imparted by AFB₁.     

Tissue disposition and excretion of 14C-labelled aflatoxin B1 after oral administration in channel catfish.

The pharmacokinetics, tissue distribution and excretion of ¹⁴C-labelled aflatoxin B₁ (AFB₁) were examined after oral administration (250 μg/kg body weight) in channel catfish (Ictalurus punctatus). Plasma concentrations of parent AFB₁ were best described by a one-compartment pharmacokinetic model, in which peak plasma concentration (503 ppb) occurred at 4.1 hr after dosing. The absorption and elimination half-lives were 1.5 and 3.7 hr, respectively. AFB₁ was highly bound (95%) to plasma proteins. Concentrations of ¹⁴C (in AFB₁ equivalents) measured in the tissues were highest at 4 hr, ranging from 596 ppb in the plasma to 40 ppb in the muscle. AFB₁ residues were rapidly depleted; at 24 hr the concentrations in the plasma and muscle were 32 and <5 ppb, respectively. Concentrations in the bile exceeded 2000 ppb (at 24 hr), whereas the highest concentration in the urine was 51 ppb (4–6-hr collection interval). Renal and biliary excretion accounted for <5% of the administered dose, indicating incomplete absorption. Pharmacokinetic modelling and tissue data demonstrate a very low potential for the accumulation of AFB₁ and its metabolites in the edible flesh of channel catfish through the consumption of AFB₁-contaminated feed.     

Central muscarinic M2 cholinoceptors involved in cholinergic hypertension

Cholinomimetic agents increase blood pressure and heart rate via central muscarinic cholinoceptors in various aspects. It was reported that i.c.v. injection of the muscarinic M₁ and M₃ cholinoceptor selective antagonist, 4-DAMP (4-diphenylacetoxy-N-methyl-piperidine methiodide, inhibited the pressor response to physostigmine, while the M₁ selective antagonist, pirenzepine, was ineffective. In the present study, the involvement of muscarinic M₂ cholinoceptors in central cholinergic hypertension and tachycardia was investigated. Physostigmine (10–80 μg/kg i.v.), a cholinesterase inhibitor, and oxotremorine (20–40 μg/kg i.v.), a direct muscarinic cholinoceptor agonist, caused a dose-dependent increase in blood pressure. Additionally, physostigmine induced dose-dependent tachycardiac responses. I.c.v. administration of the muscarinic M₂ cholinoceptor antagonists, AF-DX 116 and methoctramine, inhibited both physostigmine (60 μg/kg) and oxotremorine (20 μg/kg)-induced pressor responses at their lower doses used in this study (100 nmol/rat and 10 nmol/rat, respectively). These findings indicate the partial involvement of postsynaptic muscarinic M₂ cholinoceptors. The higher doses of the antagonists (AF-DX 116 300 nmol/rat and methoctramine 30 nmol/rat) potentiated the blood pressure increase due to physostigmine but did not affect that due to oxotremorine. The physostigmine-induced tachycardiac responses were influenced similarly by these antagonists. These results suggest the presence and tonic influence of presynaptic inhibitory muscarinic M₂ cholinoceptors.     

A comparison of matrix resolution method, ratio spectra derivative spectrophotometry and HPLC method for the determination of thiamine HCl and pyridoxine HCl in pharmaceutical preparation

A comparison of two spectrophotometric methods and a HPLC method were described in this work for the analysis of pyridoxine hydrochloride and thiamine hydrochloride in a vitamin combination. In the first method, A₁¹ (1%, 1 cm) values of these two compounds were calculated using absorbances measured at 246.8 and 290.5 nm in zero-order spectra. The matrix was written for A₁¹ (1%, l cm) values and the concentration of both compounds were determined using ‘Matlab’ software. In the second method, the measurements in the derivative of the ratio spectra were made at 297.8 and 309.5 nm for pyridoxine hydrochloride and at 245.6 and 257.7 nm for thiamine hydrochloride. The calibration graphs were established in the range 8–40 μg/ml of both vitamins. In the HPLC method, the separation of these compounds was realized on a Nucleosil 100-5 C₁₈ column with 0.1 M (NH₄)₂C0₃–water–methanol (5:15:80 v/v) as the mobile phase. Results of spectrophotometric and HPLC procedures were compared.     

安神益脑丸中黄曲霉毒素残留量测定及LC-QQQ/MS确证

目的:建立高效液相色谱-荧光检测器测定安神益脑丸中黄曲霉毒素G2、G1、B2、B1的方法;分析安神益脑丸中黄曲霉毒素的污染情况.方法:待测样品采用80％乙腈作为提取溶剂,经免疫亲和柱净化、高效液相色谱分离、光化学柱后衍生后,通过荧光检测器测定其中黄曲霉毒素的含量;采用超高效液相色谱串联三重四极杆质谱法对以上实验测定结果...     

Indian red scorpion (Buthus tamulus) venom-induced augmentation of cardiac reflexes is mediated through the involvement of peripheral 5-HT3 and central 5-HT1A receptor subtypes

The present study was undertaken to identify 5-HT receptor subtypes involved in Buthus tamulus (BT) venom-induced augmentation of cardiac reflexes elicited by phenyldiguanide (PDG). Intravenous injection of PDG (10 μg/kg) produced parallel decrease in mean arterial pressure (MAP) and heart rate (HR) in urethane anaesthetized rats (r=0.82; p<0.001). Injection of PDG (1–40 μg/kg, i.v.) produced concentration-dependent decrease in time-response area of the HR. After BT venom (20 μg/kg) the concentration-response curve was shifted to the left. Further, fall of MAP and HR in response to submaximal concentration of PDG (10 μg/kg) were augmented significantly. Pretreatment with 5-HT₃ receptor antagonist (ondansetron; 10 μg/kg) intravenously, blocked the BT venom-induced augmentation of PDG reflex but spiperone (100 μg/kg; 5-HT_1A/5-HT₂ antagonist) or ketanserin (300 μg/kg; 5-HT₂ antagonist) failed to do so. Afferent discharges elicited by PDG (10 μg/kg) in vagus nerve were doubled after exposure to BT venom. Ondansetron (100 μg/kg, i.v.) totally abolished the discharges after exposure to BT venom but not by spiperone or ketanserin. Intracerebroventricular injection of spiperone (100 μg/kg) but not ketanserin or ondansetron, blocked the BT venom-induced augmentation of PDG reflex. Results show that the BT venom-induced augmentation of reflex elicited by PDG is mediated through the involvement of 5-HT₃ receptors peripherally and 5-HT_1A type of receptors centrally.     

In vitro and in vivo biological activities of SR140333, a novel potent non-peptide tachykinin NK1 receptor antagonist

(S)1- {;2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)piperidin-3-yl]ethyl };-4-phenyl-1-azoniabicyclo[2.2.2]octane chloride (SR140333) is a new non-peptide antagonist of tachykinin NK₁ receptors. SR140333 potently, selectively and competitively inhibited substance P binding to NK₁ receptors from various animal species, including humans. In vitro, it was a potent antagonist in functional assays for NK₁ receptors such as [Sar⁹,Met(O₂)¹¹]substance P-induced endothelium-dependent relaxation of rabbit pulmonary artery and contraction of guinea-pig ileum. Up to 1 μM, it had no effect in bioassays for NK₂ ([βAla⁸]neurokinin A-induced contraction of endothelium-deprived rabbit pulmonary artery) and NK₃ ([MePhe⁷]neurokinin B-induced contraction of rat portal vein) receptors. The antagonism exerted by SR140333 toward NK₁ receptors was apparently non-competitive, with pD'₂ values (antagonism potency evaluated by the negative logarithm of the molar concentration of antagonist that produces a 50% reduction of the maximal response to the agonist) between 9.65 and 10.16 in the different assays. SR140333 also blocked in vitro [Sar⁹,Met(O₂)¹¹]substance P-induced release of acetylcholine from rat striatum. In vivo, SR140333 exerted highly potent antagonism toward [Sar⁹,Met(O₂¹¹]substance P-induced hypotension in dogs (ED₅₀ = 3 μg/kg i.v., bronchoconstriction in guinea-pig (ED₅₀ = 42 μg/kg i.v.) and plasma extravasation in rats (ED₅₀ = 7 μg/kg i.v.). Finally, it also blocked the activation of rat thalamic neurons after nociceptive stimulation (ED = 0.2 μg/kg i.v.).     

Increased motivation for beer in rats following administration of a cannabinoid CB1 receptor agonist

A series of experiments examined the effects of the cannabinoid CB₁ receptor agonist CP 55,940 ((−)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol) on the motivation to consume beer, near-beer (a beer-like beverage containing <0.5% ethanol) and sucrose solutions in rats. The experiments employed a ‘lick-based progressive ratio paradigm' in which an ever increasing number of licks had to be emitted at a tube for each successive fixed unit of beverage delivered. Break point, the lick requirement at which responding ceased, was used as an index of motivation. In the first experiment, CP 55,940 (10, 30 or 50 μg/kg) caused a dose-dependent increase in break points for beer (containing 4.5% ethanol v/v) and for near-beer. The highest (50 μg/kg) dose of CP 55,940 also significantly decreased locomotor activity. In the second experiment, CP 55,940 (10 or 30 μg/kg) dose-dependently increased break points in rats licking for ‘light' beer (containing 2.7% ethanol v/v) or for a sucrose solution (8.6% w/v) containing the same number of calories as the beer. In the third experiment, the facilitatory effects of CP 55,940 (30 μg/kg) on responding for beer and near-beer were reversed by both the cannabinoid CB₁ receptor antagonist SR 141716 (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride) (1.5 mg/kg) and the opioid receptor antagonist naloxone (2.5 mg/kg). Naloxone had a proportionally greater effect on rats licking for beer compared to near-beer, consistent with previous reports of opioid receptor mediation of alcohol craving. These results show that cannabinoids modulate the motivation for beer via both cannabinoid CB₁ receptors and opioid receptors. The similar effect of CP 55,940 on the motivation for beer, near-beer and sucrose suggests that the drug effect may reflect a general stimulatory effect on appetite for palatable beverages, although a more specific effect on the desire for alcohol cannot be ruled out.     

A pharmacological examination of venom from the Papuan taipan (Oxyuranus scutellatus canni).

The Papuan taipan (Oxyuranus scutellatus canni) is the third most venomous terrestrial snake in the world, however, little is know about the pharmacology of the venom. In the chick biventer cervicis muscle, venom (10 μg/ml) abolished nerve-mediated twitches (time to 90% inhibition (t₉₀) 44±5 min, n=9). This inhibition was unaffected by prior incubation of the venom with the phospholipase A inhibitor 4-bromophenacyl bromide (4-BPB; 0.72 mM) (t₉₀ 48±7 min, n=8). The mouse phrenic nerve diaphragm preparation displayed greater sensitivity to venom (10 μg/ml) (t₉₀ 25±1 min, n=6). In the chick biventer muscle, venom (10 μg/ml) significantly inhibited responses to acetylcholine (1 mM) and carbachol (20 μM), but not KCl (40 mM), indicating activity at post-synaptic nicotinic receptors. Venom (10 μg/ml) did not affect direct muscle stimulation. Venom (3–30 μg/ml) produced dose-dependant contractions of the guinea-pig ileum. Contractile responses were significantly inhibited by indomethacin (1 μM) or prior incubation of the venom with 4-BPB (0.72 mM) indicating involvement of a PLA component. In rat phenylephrine (0.3 μM) precontracted aortae, venom (3–100 μg/ml) produced endothelium-independent relaxation which was unaffected by prior incubation of venom (30 μg/ml) with 4-BPB (0.72 mM). In anaesthetised rats, 10 μg/kg (i.v.) venom produced rapid respiratory and cardiovascular collapse while 5 μg/kg (i.v.) venom produced only a small transient decrease in mean arterial blood pressure. Prior administration of 5 μg/kg (i.v.) venom enabled subsequent administration of 10 and 100 μg/kg (i.v.) venom without respiratory or cardiovascular collapse. Further work is required to identify specific toxins with the above pharmacological activity.     

Studies on the in vitro metabolism of aflatoxin B1 and G1 in the liver of rats fed at various levels of vitamin C

Male and female weanling rats, divided into three groups, were maintained for 30, 60 and 90 days on an experimental diet without vitamin C. The drinking water containing or devoid of vitamin C was offered each day. The first group had no vitamin C; the second group or control had normal vitamin C and the third group had above-normal vitamin C in the water. Twenty-four hours after the last feeding, the animals were decapitated and the liver microsomes plus soluble fraction (9000 g) were prepared. This preparation was used for O-demethylase and the hydroxylase assays of aflatoxins B₁ and G₁ (AFB₁ and AFG₁). Results from O-demethylation in both control and experimental groups of both sexes, showed that O-demethylase activity is directly related to ascorbic acid content of the water. But the hydroxylase activity in male and female animals maintained on the same diet showed only slight differences. In the male, there was an increase with time of hydroxylase activity with AFB₁ up to 60 days and a decrease at 90 days. Hydroxylation assay revealed that in the female, metabolism of AFB₁ increased at 30 days but decreased at 60 and 90 days.     

Effect of atropine on cyanide-induced acute lethality in mice

The effects of atropine on acute lethality induced by cyanide were investigated in mice. The LD₅₀ value of cyanide (s.c. injection) was 8.4 (7.6–9.3) mg/kg. However, the LD₅₀ value of cyanide (s.c.) was significantly increased by 1.5-fold when atropine (32 mg/kg) was injected s.c. in mice. Furthermore, the combined administration of atropine (32 mg/kg). Ca²⁺ (500 mg/kg) and sodium thiosulfate (1 g/kg) tremendously increased the LD₅₀ value by 5.6-fold in mice although sodium thiosulfate or Ca²⁺ alone increased the LD₅₀ 2.5- or 1.5-fold. On the other hand, although the LD₅₀ value of cyanide (intracerebroventricular injection (i.v.t.)) was 52.0 (47.4–57.0) μ/brain, the LD₅₀ value of cyanide (i.v.t.) was significantly increased by 1.3- or 1.61-fold in mice 10 min after s.c. injection of atropine (32 mg/kg) or Ca²⁺ (500 mg/kg). Furthermore, the combined administration of atropine and Ca²⁺ increased the LD₅₀ value of cyanide by 2.1-fold. These results suggest that atropine inhibits cyanide-induced acute lethality and promotes the antagonistic effect of thiosulfate and Ca²⁺ in mice.     

Identification and analysis of absorbed and metabolic components in rat plasma after oral administration of 'Shuangdan' granule by HPLC-DAD-ESI-MS/MS

A valid method using liquid chromatography–diode array detection–electrospray ionization (ESI) ion trap mass spectrometry was established for the study of the absorbed and metabolic components of a Chinese medicine ‘Shuangdan’ granule in rat plasma after oral administration. The plasma samples were acidified with 1 M hydrochloric acid and extracted with ethyl acetate (EtOAc) of two-fold volume for three times. The chromatographic separation was carried out on a Zorbax SB-C₁₈ column with a linear gradient whereas 0.1% acetic acid/water/acetonitrile was used as mobile phase. Mass spectra were acquired in both negative and positive modes. More than 20 components including 16 components from ‘Shuangdan’ granule and 5 metabolites were simultaneously identified by comparing their mass spectra and retention behavior with reference compounds or literature data. The results proved that the established method could be used to identify the structure of active components responsible for the pharmacological effects of ‘Shuangdan’ granule.     

Supraspinal mu 2-opioid receptors mediate spinal/supraspinal morphine synergy.

TRIMU-5 (Tyr-D-Ala-Gly-NHC₂H₄CH(CH₃)₂) is a potent μ₂-opioid agonist/μ₁-opioid antagonist. A supraspinal dose (0.5 μg i.c.v.) of TRIMU-5 which is not analgesic when given alone antagonizes the analgesia produced by intracerebroventricular (i.c.v.) morphine, a μ₁ action. In contrast, in a synergy model consisting of the simultaneous administration of intrathecal morphine (0.1 μg) with multiple doses of i.c.v. morphine, the same supraspinal TRIMU-5 dose (0.5 μg i.c.v.) enhances analgesia. Supraspinal TRIMU-5 also potentiates spinal morphine directly, shifting its dose-response to the left. These results imply that within the brainstem μ₁ receptors mediate supraspinal analgesia while μ₂ receptors mediate the synergy with spinal μ systems.     

Determination of tyramine in cheese by LC-UV

An isocratic reversed-phase liquid chromatographic assay for tyramine has been developed. The method is based on the reaction of tyramine with 4-chloro-7-nitrobenzofurazan and measurement of the absorbance at 458 nm after chromatographic separation on a C-18 column. Optimum reaction conditions were investigated. A linear relationship was found between absorbance and concentration over the range 25–300 ng per 10 μl of tyramine. The method was applied to the determination of tyramine in cheese. The cheese sample was homogenized with 5% (w/v) HClO₄ extracted with ethyl acetate–acetone (2:1) and chromatographed on high performance liquid chromatography (HPLC) after derivatization reaction with NBD-Cl. The determination limit was 25 μg/g cheese. The mean recovery of tyramine from cheese was 98.0%.     

Effects of adenosine A2 receptor agonists on the excitation of capsaicin-sensitive afferent sensory nerves in airway tissues

We examined the effects of adenosine analogues on the asthmatic reactions induced by the stimulation of capsaicin-sensitive afferent sensory nerves. Intravenous (i.v.) injection of adenosine A₂ receptor agonists, 5′-(N-ethylcarboxamido)-adenosine (NECA) and 2-[p-(carboxyethyl)-phenylethylamino]-5′-N-ethylcarboxamido-adenosine (CGS 21680), dose dependently inhibited capsaicin-induced guinea-pig bronchoconstriction (1–1000 nmol kg⁻¹), whereas i.v. administration of the adenosine A₁ receptor agonist, N⁶-cyclo-hexyladenosine (CHA), did not affect it (1000 nmol kg⁻¹). Intratracheal injection of NECA (0.05–5 nmol site⁻¹) and CGA 21 680 (0.05−5 nmol site⁻¹) also reduced capsaicin-induced constriction in a dose-dependent manner. However, NECA (1000 nmol kg⁻¹) failed to inhibit substance P-induced guinea-pig bronchoconstriction. NECA (1–1000 nmol kg⁻¹) dose-dependently inhibited cigarette smoke-induced rat tracheal plasma extravasation, but not substance P-induced reaction. NECA (0.1–10 μM) and CGS 21 680 (10 μM) significantly blocked the capsaicin-induced release of substance P-like immunoreactivity from guinea-pig lung, whereas CHA (10 μM) had no effect. This evidence suggests that adenosine A₂ receptors modulate negatively the excitation of capsaicin-sensitive afferent sensory nerves and substance P release from their endings in airway tissues.     

Stability-indicating methods for the determination of sumatriptan succinate

Four stability-indicating methods were developed for the determination of sumatriptan succinate in the presence of its degradation products. The first method depends on the quantitative densitometric evaluation of thin-layer chromatography of sumatriptan succinate in the presence of its degradation products without any interference. Cyclohexane–dichloromethane–diethylamine (50:40:10 v/v/v) was used as a mobile phase and the chromatogram was scanned at 228 nm. This method determines sumatriptan succinate in the concentration range l–8 μg per spot with mean percentage recovery 100.52±1.23%. The second and third methods depend on the use of first-derivative (D₁) and second-derivative (D₂) spectrophotometry at 234 and 238 nm, respectively. These methods determine the drug in the concentration range 1.25–10 μg ml⁻¹ with mean percentage recovery 99.91±1.01% and 99.96±1.13% for (D₁) and (D₂), respectively. The fourth method depends on the use of ratio derivative spectrophotometric technique. The amplitude in the first derivative of the ratio spectra at 235 nm was selected to determine the cited drug in the presence of its degradation products. Calibration graph is linear in the concentration range 1.25–10 μg ml⁻¹ with mean percentage recovery 100.19±1.19%. The suggested methods were successfully applied for determining sumatriptan succinate in bulk powder, laboratory-prepared mixtures and pharmaceutical dosage forms (Imigran tablet) with good accuracy and precision. The results obtained by applying the proposed methods were statistically analyzed and compared with those obtained by the reported method.     

A capillary GC-MS method for analysis of phenytoin and [C3]-phenytoin from plasma obtained from pulse dose pharmacokinetic studies

Stable isotope analogues of phenytoin are useful for pulse dose pharmacokinetic studies in epilepsy patients. A simultaneous assay was developed to quantitate phenytoin (5,5-diphenylhydantoin) and its stable isotope analogue [¹³C₃]-phenytoin (5,5-diphenyl-2,4,5-¹³C₃-hydantoin) from plasma. Quantitation was achieved by GC-MS analysis of liquid/liquid extracted plasma samples, with [²H₁₀]-phenytoin (5,5-di(pentadeuterophenyl)-hydantoin) as an internal standard. The total coefficients of variance (C.V._t) were <7% for phenytoin (2.5–40 μg ml⁻¹) and <10.3% for [¹³C₃]-phenytoin (0.1–6.0 μg ml⁻¹). The accuracy of the assay varied from 87.8–100.1% (phenytoin, 2.5–40 μg ml⁻¹) and 89.6–116.3% ([¹³C₃]-phenytoin, 0.02–6.0 μg ml⁻¹). The assay was tested under in vivo conditions by administration of a pulse dose of the stable isotope analogue to a single rat dosed to steady-state with fosphenytoin, a phenytoin prodrug. The results of the in vivo experiment demonstrate the usefulness of this assay for future pharmacokinetic studies in special population epilepsy patients.     

Interference by the novel PAF-acether antagonist WEB 2086 with the bronchopulmonary responses to PAF-acether and to active and passive anaphylactic shock in guinea-pigs

The interaction between the triazolothienodiazepine WEB 2086 and the in vitro and in vivo bronchopulmonary effects of PAF-acether and active/passive anaphylaxis in the guinea-pig was studied. WEB 2086 (1–100 nM) inhibited PAF-acether (10–100 ng)-induced bronchoconstriction and TXB₂ release from isolated and perfused guinea-pig lungs without affecting the response to 100 μg arachidonic acid. In addition, 1–10 μM WEB 2086 significantly reduced antigen-induced TXB₂ and histamine release from lungs from actively and passively sensitized guinea-pigs. In the presence of the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA), mepyramine, methysergide, indomethacin and atropine, WEB 2086 (20–50 μM) inhibited by 30–40% the residual contraction of lung parenchyma strips from guinea-pigs actively sensitized by 0.1–10 μg antigen. In vivo, WEB 2086 (0.1–1 mg/kg) reversed or abolished the bronchoconstriction, hypotension, thrombocytopenia and leukopenia evoked by perfusion of PAF-acether (3 or 44 ng/kg per min). At 3 mg/kg, WEB 2086 also markedly decreased the bronchoconstriction and leukopenia induced by 100 μg/kg antigen in mepyramine (5 μg/kg)-treated passively sensitized guinea-pigs. In contrast, WEB 2086 was ineffective against active anaphylaxis in vivo. These results demonstrate that WEB 2086 antagonizes the bronchopulmonary effects due to PAF-acether and to anaphylactic shock in the guinea-pig.