Gas chromatographic mass analysis and further pharmacological actions of Cymbopogon proximus essential oil.

The present study reports Gas chromatographic mass analysis (GC-MS) as well as important biological activities of Cymbopogon proximus essential oil. The chemical composition of the essential oil of Cymbopogon proximus was investigated by GC-MS. Furthermore, the effects of Cymbopogon proximus essential oil on the cardiac parasympathetic ganglia in rats, the intra-tracheal pressure in guinea-pigs and on carrageenan-induced inflammation in the rats paw, were studied. The GC-MS study led to the identification of 22 components with Piperitone representing (73.81%), Elemol (9.32%), alpha-Eudesmol (5.21%) and alpha-Terpineol (3.01%) of the oils composition. The percentage protective effect of the oil on the vagus-induced bradycardia in rats was 90.1±3.1%, which represents a significant protection. As for the effect of Cymbopogon oil on bronchoconstrictors-induced increase in intra-tracheal pressure in guinea-pigs, the oil antagonized the actions of 5-HT and histamine by 80±3.7 and 93±8.3%, respectively. Pharmacological investigations using Cymbopogon oil revealed its inherent ability to possess a bronchodilator activity mediated via blockade of both histamine and serotonin receptors. It possessed a significant ganglionic blocking action and a limited anti-inflammatory activity that seemed to involve blockade of histamine and serotonin receptors in the rats' paws.

Pharmacological studies on Myrica rubra Sieb et zucc. Effects on the cardiovascular system and platelets.

UNLABELLED: The effects of 50% Drink of Myrica rubra (MRD) on the cardiovascular system of the rat and on the platelets aggregation of rats and guinea pigs were studied. METHOD: Different groups of male Wistar rats were treated either with 50% Myrica rubra drink as drinking vehicle (4 weeks) or water. The animals were then prepared for the measurement of arterial blood pressure and heart rate, ECG, sensitivity of the baroreceptors, platelets' aggregation, blood clotting time and cardiac parasympathetic ganglia. The mechanism of action of any induced effect was elucidated using different receptor blockers. RESULTS: Treatment induced a significant decrease in the arterial blood pressure and heart rate on Wistar rats, but no significant changes in the ECG were observed. Pretreatment of rats with MRD 10 or 20 ml/kg (i. p.) significantly suppressed vagal electrical stimulation to the heart and nicotine-induced bradycardia, via decreasing phenylephrine-induced rise in the arterial blood pressure and the reflexly-induced bradycardia. It significantly suppressed the Baroreceptor Sensitivity Index (BSI). The treatment also significantly suppressed ADP-induced platelets aggregation in rats and arachidonic acid-induced aggregation in guinea pigs.All these actions seemed to be mediated by the MRD constituents such as proanthocyanidins, polyphenols and flavonoids. The decreases in the heart rate and BSI were probably caused by an inherent ability to block the parasympathetic ganglia. CONCLUSION: The results of this study regarding the effects of MRD actions on the cardiovascular system and platelets qualify the drink to be classified as a functional food.

Studies on the cardiovascular depressant effects of N-ethyl- and N-benzyl-1,2-diphenylethanolamines in the rat: elucidation of the mechanisms of action.

The influence and mechanisms of action of N-ethyl- and N-benzyl-1,2-diphenylethanolamines (compounds E and B, respectively) on the arterial blood pressure and the heart rate of the rat together with their effects on CaCl2-induced arrhythmias in the rat were investigated. Both E and B in doses of (1.5-12 micromol/kg IV) decreased the arterial blood pressure and the heart rate in a dose-dependent manner. Studies with various receptor blockers, enzyme inhibitors and CaCl2 revealed that E-induced cardiovascular depressant effects were mainly due to CaCl2 channel blocking action and activation of cyclic guanylyl cyclase or release of NO whereas the cardiovascular effects of B seemed to involve both blockade of Ca2+ channels and activation of parasympathetic ganglia. Both compounds (12-14.5 micromol/kg) completely protected the rat against CaCl2 (60 mg kg(-1))-induced tachyarrhythmias. The B compound seemed to be several times more potent than the E compound in its cardiovascular depressant actions. The results suggest the potential usefulness of both compounds in the treatment of hypertension and supraventricular arrhythmias.

Studies on the spasmolytic and uterine relaxant actions of n -ethyl and n -benzyl-1,2-diphenyl ethanolamines: elucidation of the mechanisms of action.

The influence of N -ethyl- and N -benzyl-1,2-diphenyl ethanolamines (compounds E and B, respectively) was examined on the spontaneously contracting rabbit jejunum and the rat uterus together with their influence on the contractions induced by some spasmogens in the guinea-pig ileum and oxytocics and CaCl2in the pregnant rat uterus. Both E and B inhibited the spontaneous contractions of the rabbit jejunum with ID50values of 0.13 and 0.03 micromol ml-1. Their inhibitory activities were not antagonized by alpha- or beta-adrenoceptor blockers but significantly reversed by CaCl2(0.015 micromol ml-1). The compounds also antagonized nicotine, ACh-, histamine-, 5-HT- and CaCl2-induced contractions by 44-100%. Compound E seemed to be several times more potent than B in inhibiting the spontaneous uterine contractions with an ID50of (7 nmol ml-1). Their inhibitory effects were not antagonized by beta2-adrenoceptor or H2-receptor blocking drugs. Both compounds (40 nmol ml-1) antagonized in a competitive manner CaCl2-induced contractions in the K+-depolarised uterus and PGE2and oxytocin-induced uterine contractions. The ID50values were in the range of 1.6-10.7 nmol ml-1. The results suggest that E and B compounds may be considered as putative L-Ca2+channel blockers with certain selectivities. The E compound seemed to be more selective against uterine L-Ca2+channels and the B compound against intestinal smooth muscles. Thus, the compounds may be of potential value in treatment of some colics, the irritant bowel syndrome, dysmenorrhoea and premature deliveries.

The pharmacological effects of some 1H-1,4-benzothiazineylide derivatives on the cardiovascular system of the rat and some smooth muscles.

A series of 1H-1,4-benzothiazineylides was synthesized and characterized. The influence of this series of compounds 1-7 was examined on the cardiovascular system of the rat, the isolated jejunum of the rabbit, the guinea-pig ileum and the isolated uteri of late pregnant rats. The results of the present study revealed the bradicardiogenic effect of the ethyl, propyl and isobutyl derivatives when tested in the dose range of (10-53 mumole Kg-1). Furthermore, the isobutyl derivative also exhibited an ability to decrease the arterial blood pressure. All the test compounds exhibited non-spasmolytic activity against ACh, histamine and BaCl2. The butyl, isobutyl and isopropyl derivatives were found to be the most potent. The results direct the attention to a new potential group of cardiovascular depressant and spasmolytic agents.

Cardiovascular effects of some 2-substituted triazolo[1,5-a]pyrimidin-7(4H)one-6-carboxylic acid ethyl esters.

The cardiovascular effects of a series of 2-substituted- 1,2,4-triazolo[1,5-a]-pyrimidine derivatives (compounds 1-6) were examined in anaesthetized rats. Of these compounds only compounds 3 and 4 in dose of (15-60 mumole/Kg) induced dose-dependent decreases in the arterial blood pressure and heart rate. The induced cardiovascular changes were not antagonised by histaminergic, cholinergic, serotoninergic receptor blockers, prostaglandin synthesis inhibitors or Cacl2. Treatment of the animals with the compounds (20-30 mumole/Kg) competitively antagonised noradrenaline-induced increase in the arterial blood pressure and significantly antagonised isoprenaline-induced tachycardia but not the induced hypotension. The compounds seemed to possess both alpha 1- and, beta 1-adrenoceptor blocking activities.

The respiratory effects of the volatile oil of the black seed (Nigella sativa) in guinea-pigs: elucidation of the mechanism(s) of action.

1. The effect of the volatile oil (VO) of the black seed (Nigella sativa) on the respiratory system of the urethane-anaesthetized guinea-pig was investigated and compared with those of its constituent thymoquinone (TQ). 2. Intravenous administration of VO in the dose range (4-32 microliters kg-1) induced dose-dependent increases in the respiratory rate and the intratracheal pressure. 3. The effects of VO were significantly antagonized by treatment of the animals with mepyramine, atropine and reserpine. They were not antagonized by indomethacin, diethyl carbamazine or hydrocortisone. 4. Intravenous administration of TQ in the dose range (1.6-6.4 mg kg-1) induced significant increases in the intratracheal pressure without any effect in the respiratory rate. 5. The results suggested that VO-induced respiratory effects were mediated via release of histamine with direct involvement of histaminergic mechanisms and indirect activation of muscarinic cholinergic mechanisms. 6. Removal of TQ from VO may provide a potential centrally acting respiratory stimulant.

The cardiovascular actions of the volatile oil of the black seed (Nigella sativa) in rats: elucidation of the mechanism of action.

1. The effects of the volatile oil (V.O.) of the black seed (Nigella sativa) on the arterial blood pressure and heart of urethane-anaesthetized rats were investigated and the effects were compared with those of its constituent thymoquinone (T.Q.). 2. Intravenous administration of V.O. in the dose range (4-32 microliters kg.-1) or T.Q. (0.2-1.6 mg kg-1) to rats decreased the arterial blood pressure and the heart rate in a dose-dependent manner. 3. The effects of V.O. were significantly antagonized by treatment of the animals with cyproheptadine, hexamethonium atropine and by spinal pithing. 4. Treatment of the animals with reserpine (5 mg kg- 1 day-1 for 2 days) significantly antagonized the cardiovascular depressant effects induced by 4 and 8 microliters of V.O. kg-1 but not those induced by the larger doses. 5. T.Q.-induced cardiovascular depressant effects were significantly antagonized by atropine and cyproheptadine but not by reserpine. 6. The results suggested that V.O.-induced cardiovascular depressant effects were mediated mainly centrally via indirect and direct mechanisms that involved both 5-hydroxytryptaminergic and muscarinic mechanisms. The direct mechanisms may be due to the presence of T.Q. in the V.O. The V.O. seemed to possess the potential of being a potent centrally acting antihypertensive agent.

Effect of praziquantel and oxamniquine on prostacyclin synthesis by the rat arterial and myometrial tissues.

1. The influence of the two antischistosomal drugs (+/-) praziquantel and (+/-) oxamniquine on PGI2 synthesis by the male rat thoracic aorta and day-20 pregnant rat myometrium in vitro was investigated using a rat platelet antiaggregatory bioassay method. 2. Pretreatment of the tissues with praziquantel (64-512 microM) or oxamniquine (36-288 microM) for 30 min at 37 degrees C significantly inhibited basal PGI2 synthesis in a concentration-dependent manner (P less than 0.005, n = 5-6). 3. Both drugs failed to inhibit PGI2 synthesis in presence of exogenous arachidonic acid (AA) (16.6 microM). 4. Furthermore, they did not antagonize AA (4 nmol kg-1)-induced hypotension in urethane-anaesthetized rats. Thus, the drugs seemed to act via inhibition of phospholipase A2 enzyme (PLA2). 5. The highly lipophilic drugs may interact with membrane phospholipids resulting in prevention of interaction between the substrates and the enzyme's active site.

Influence of chemotherapeutic agents on prostacyclin synthesis. II. Effects of tetracycline and penicillin G on prostacyclin synthesis by the rat thoracic aorta and myometrial tissues.

The influence of the two antibiotics tetracycline hydrochloride (T) and penicillin G sodium (P) on PGI2 synthesis by the male rat thoracic aorta and day-20 pregnant rat myometrium was investigated in vitro using a rat platelet antiaggregatory bioassay method. Pretreatment of the tissues for 30 min at 37 degrees C with T (21-168 microM) or P (28-224 microM) significantly inhibited PGI2 synthesis in absence or presence of exogenous arachidonic acid (AA) (16.6 microM), (P less than 0.01, n = 5-6). Furthermore, pretreatment of rats with the two drugs (T 11 and P 175 mu mole kg-1 for 30 min) significantly antagonised AA (4 n mole kg-1)-induced hypotension in urethane-anaesthetised rats. They also (T 0.5-4 and P 1-6 microM) antagonised AA-induced aggregation in rabbit citrated platelet-rich plasma. T failed to affect ADP-induced aggregation to any significant level whereas P (3-6 microM) reduced ADP-induced aggregation. The drugs seemed to interfere with the action of the PG endoperoxide synthase (or PG cyclooxygenase) enzyme resulting in decreased formation of PGG2 and PGH2. Such an effect may have resulted from the induced formation of toxic [OH-] radicals and/or inhibition of O2 uptake by the tissues under the influence of the drugs. The demonstrated inherent property of these two antibiotics to inhibit the synthesis of the potent vasodilator, platelet antiaggregatory, anticonvulsant and inhibitor of gastric acid secretion--PGI2, may partly contribute towards better understanding of the biochemical mechanisms that underlie some of the previously known but poorly understood actions of these antibiotics. Furthermore, since good evidence exists for the involvement of excessive uterine prostaglandin synthesis in dysmenorrhoea and premature deliveries, it is suggested that the potential benefits of T or P in these two disorders be investigated.

Effects of N-methyl- and N-isobutyl-1,2-diphenyl ethanol amines on the spontaneous and evoked contractions in the rat isolated uterus.

1. The effects of N-methyl- and N-isobutyl-1,2-diphenyl ethanol amine (compounds M & E), respectively and diltiazem (D) were examined on the spontaneous and evoked uterine contractions of pregnant rats in vitro. 2. Addition of compound M (75-300 microM), compound E (15-60 microM) or D (100-400 nM) to the uterine tissues, inhibited the spontaneous contractions in a dose-dependent manner. The potency order was D greater than E greater than M. 3. The inhibitions were reversed by elevating the extracellular Ca2+ concentration by 20 mM. The compounds also antagonised CaCl2-evoked contractions. 4. Treatment of rats with either compound during pregnancy days (1-16) did not affect the implantation process and did not induce any teratogenicity. 5. The uterine inhibitory effects of the compounds may be due to blockade of uterine Ca2+ channels.

Cardiovascular depressant effects of N-methyl- and N-isobutyl-1,2-diphenyl ethanolamines: elucidation of the mechanisms of action.

The cardiovascular effects of N-methyl-1,2-diphenyl ethanolamine (compound M) and N-isobutyl-1,2-diphenyl ethanolamine (compound E) were examined in anaesthetized rats and their effects were compared with those of verapamil and diltiazem. Administration of compound M (10-80 mumole/kg), compound E (2-16 mumole/kg), diltiazem (1.5-24 mumole/kg) or verapamil (1.25-10 mumole/kg) induced dose-dependent decreases in arterial blood pressure and heart rate. The induced cardiovascular changes were not antagonized by chlorpheniramine, cimetidine or imidazole. Indomethacin antagonized the diltiazem-induced hypotension without any effect on that of compounds M and E. The effects of all compounds tested were antagonized by pretreatment of the rats with CaCl2 (1.2-2.4 mmole/kg). Furthermore, methylene blue significantly antagonized the compound E- and diltiazem-induced hypotension. Treatment of the animals with propranolol enhanced the compound M- and E-induced hypotension. Compounds M and E antagonized the NA-induced increase in arterial blood pressure in a competitive manner. Compounds M and E seem to exert their cardiovascular effects via interference with the influx of extracellular Ca2+. Furthermore, compound E and diltiazem may act partially via activation of guanylyl cyclase.

Influence of diethylcarbamazine and mefloquine on PGI2 synthesis by the rat thoracic aorta and myometrial tissues.

1. The influence of the antifilarial drug diethylcarbamazine citrate (D) and DL-erythro mefloquine hydrochloride (Mf) on PGI2 synthesis by the male rat thoracic aorta and day-20 pregnant rat myometrium was investigated in vitro using a rat platelet antiaggregatory bioassay method. 2. Pretreatment of the tissues with D (25.5-204 microM) or Mf (24-192 microM) for 30 min at 37 degrees C significantly inhibited PGI2 synthesis in a concentration-dependent manner. 3. D exhibited its inhibitory effect even in presence of exogenous arachidonic acid (AA) (16.6 microM) whereas Mf lost its inhibitory effect in presence of AA. 4. Pretreatment of urethane-anaesthetized rats with D (32 mumol kg-1) but not Mf (7.5 mumol kg-1) for 30 min significantly antagonized AA (4 nmol kg-1)-induced hypotension. 5. Furthermore, D (0.25-0.5 microM) antagonized AA-induced aggregation in rabbit platelet-rich plasma without affecting that of ADP. 6. D seemed to interfere with the action of the PG endoperoxide synthase (PG cyclooxygenase) whereas Mf seemed to interfere with the action of phospholipase A2 (PLA2) enzyme. 7. D may have exerted its effect via release of toxic O2 radicals whereas Mf effect may have been due to an interaction with PLA2 substrate phospholipids. 8. The demonstrated inherent property of these two drugs to inhibit the synthesis of the potent vasodilator, platelet antiaggregatory, anticonvulsant and antiinflammatory mediator PGI2 may partly contribute towards better understanding of the biochemical mechanisms that underly some of the previously known but poorly understood actions of these drugs.

Antiaggregatory activity of N-methyl- and N-isobutyl-1,2-diphenyl ethanolamines in rat platelets.

The ability of N-methyl-1,2-diphenyl ethanolamine (compound M), N-isobutyl-1,2-diphenyl ethanolamine (compound E), diltiazem and verapamil to inhibit in vitro ADP-induced platelet aggregation was examined in rat platelet-rich plasma. Pretreatment of the platelets with the compounds (0.1-3 mM) for 3 min at 37 degrees C, inhibited an ADP-induced aggregation in a concentration-dependent manner. The maximum percentage inhibitions induced by compounds M, E, diltiazem and verapamil were: 95.5 +/- 6.5, 98.4 +/- 7.5, 100 and 95.9 +/- 8.3% at concentrations of 3, 0.64, 0.96 and 0.4 mM, respectively (n = 8 - 12). The inhibitory dose 50 (ID50) values for compounds M, E, diltiazem and verapamil were 1.3 +/- 0.13, 0.29 +/- 0.01, 0.44 +/- 0.03 and 0.2 +/- 0.01 mM, respectively. The antiaggregatory effects were not antagonized by methylene blue (50-200 microM), but were completely antagonized (greater than 95%) by elevation of the Ca2+ level in the platelet-rich plasma by 0.2-0.7 mM. Co-administration of (-)propranolol (17 microM) with anyone of the compounds enhanced the antiaggregatory effects. The compounds (0.1-0.2 mM) enhanced the prostacyclin (0.01 nM)-induced antiaggregatory activity. The antiaggregatory effects of the compounds are likely to be due to an inhibition of influx of Ca2+ into the platelets.

Influence of tea and coffee beverages on prostacyclin synthesis by the rat aorta.

Influences of 2.5 and 5% (w/v) aqueous tea and coffee beverages administered ad lib. to rats for two weeks on PGI2 synthesis by the rat thoracic aorta in vitro were investigated using a rat platelet antiaggregatory bioassay and HPLC methods. The 2.5% beverages did not affect PGI2 synthesis; however, the 5% beverages significantly decreased PGI2 synthesis. The observed decreases were significantly abolished in presence of exogenous arachidonic acid suggesting a beverage-induced inhibition of precursor release. The ability of the beverages to inhibit PGI2 synthesis may partly contribute towards better understanding of the biochemical mechanisms underlying some of the beverages-induced actions in vivo.

The antiarrhythmic activity of N-alkyl-1,2-diphenylethanolamines.

The activity of N-alkyl-1,2-diphenylethanolamines against CaCl2-induced cardiac arrhythmia was evaluated in the rat. The potencies of the compounds were compared with that of the established calcium ion-channel blocker, verapamil. The N-methyl, N-ethyl, and N-isobutyl derivatives as well as verapamil at doses of 2-8 mumols kg-1 protected the animals against the induced arrhythmia. The potency order was verapamil greater than N methyl greater than N-ethyl greater than N-isobutyl derivatives. The N-isopropyl and N-butyl derivatives were inactive. The antiarrhythmic activity of the compounds was not due to local anesthetic activity but may be caused by calcium-channel inhibition.

Influence of alpha-tocopherol on prostacyclin synthesis by rat's arterial and myometrial tissues.

Influence of alpha-tocopherol on PGI2 synthesis by rat arterial and myometrial tissues was investigated using a rat platelet antiaggregatory bioassay. Chronic administration of alpha-tocopherol to female rats (10 mg kg-1 day-1 s.c. for 14 days) significantly increased ex-vivo PGI2 synthesis by the arterial tissue from 12.7 +/- 0.3 (control, mean +/- s.e.m) to 17.2 +/- 0.4 ng PGI2 mg-1 wet tissue and by the myometrial tissue (in proestrus) from 1.1 +/- 0.07 (control) to 1.85 +/- 0.1 ng PGI2 mg-1 wet tissue (P less than 0.05, n = 6). alpha-tocopherol (5 mg kg-1 day-1 for 14 days) did not stimulate PGI2 to any significant level. Pretreatment of male rat arterial tissue with alpha-tocopherol (0.02, 0.1 or 0.2 mM) in vitro increased PGI2 synthesis in a dose-dependent manner. At a dose of 0.2 mM it increased PGI2 synthesis from 13.70 +/- 0.70 (control) to 22.6 +/- 1.4 ng PGI2 mg-1 wet tissue (P less than 0.1, n = 6). Pre-treatment of 14-day pregnant rat myometrium with alpha-tocopherol 0.2 and 0.4 mM significantly increased PGI2 synthesis from 1.2 +/- 0.06 (control) to 1.90 +/- 0.12 and 2.1 +/- 0.1 ng PGI2 mg-1 wet tissue, respectively (P less than 0.05, n = 6). The results indicate that the ability of alpha-tocopherol to stimulate PGI2 synthesis may partly contribute towards better understanding of the mechanisms that underly the protective effect of alpha-tocopherol against experimentally induced decreases in coronary flow and intravascular coagulations in some mammals. Furthermore adequate intake of alpha-tocopherol during pregnancy may enhance uterine blood flow and ensure adequate foetal nutrition.

Effects of sesame and cod liver oils on prostacyclin synthesis by the rat thoracic aorta.

The influence of sesame and cod liver oils (0.5 and 1 g/kg/day s.c. for 2 weeks) on arterial PGI2 synthesis in the rat was investigated using a rat platelet antiaggregatory bioassay and HPLC methods. Smaller doses did not affect PGI2 synthesis. However, sesame oil at a dose of 1 g/kg/day significantly stimulated PGI2 synthesis, whereas cod liver oil at the same dose significantly decreased the synthesis. Incubation of control tissues in presence of exogenous arachidonic acid (33 microM) significantly stimulated PGI2 synthesis, however, incubation of cod liver oil-treated tissues in presence of arachidonic acid resulted in PGI2 synthesis, similar to that observed in the nontreated controls. The changes observed in PGI2 synthesis in the tissues from oil-treated rats may have resulted from modulation in arachidonic acid release and/or direct effects on the enzymes involved in PGI2 synthesis. The oil-induced changes in PGI2 synthesis may partly contribute towards better understanding of the biochemical mechanisms that underly some of the in vivo actions of these oils.

Influence of bromocriptine on free amino acids in the kidneys and heart of the rat.

The effects of bromocriptine, sulpiride or their combination on free amino acids in the kidneys and the heart after acute and chronic treatment of rats were investigated, using an automatic LKB Amino Acid Analyzer. Bromocriptine at a single dose of 4 or 10 mg/kg (i.p.) did not affect the level of any amino acid; however, at a dose of 20 mg/kg it significantly elevated the content of taurine in the kidney from 7.00 +/- 0.30 to 9.70 +/- 0.1 and in the heart from 22.9 +/- 1.7 to 30 +/- 1.2 mumol/g wet tissue (P less than 0.05, N = 7). It also increased glutamic acid in the heart from 3 +/- 0.1 to 4.5 +/- 0.25 mumol/g wet tissue (P less than 0.05, N = 7). Chronic oral treatment of rats with bromocriptine (20 mg.kg-1.day-1) for 5 weeks significantly elevated the level of taurine in the kidney from 7.2 +/- 0.3 (control) to 11.1 +/- 0.90 and in the heart from 23.1 +/- 1.7 to 38.8 +/- 1.8 mumol/l g wet tissue. It also increased cardiac glutamic acid content from 3 +/- 0.1 to 4.8 +/- 0.24 mumol/g wet tissue (P less than 0.01, N = 7). Concurrent administration of sulpiride (20 mg/kg) significantly suppressed bromocriptine-induced increases in taurine and glutamic acid in both organs, suggesting an activation of D2 receptors by bromocriptine. Due to the similarities between bromocriptine and the affected amino acids in renal and cardiac actions, it is suggested that mobilization of taurine and glutamic acid may at least in part contribute towards bromocriptine-induced renal and cardiac actions.

Influence of niridazole and chloroquine on arterial and myometrial prostacyclin synthesis.

1. The effects of niridazole and chloroquine on rat arterial and myometrial prostacyclin (PGI2) synthesis in vitro were investigated by use of a rat platelet antiaggregatory bioassay. Niridazole (233 microM) and chloroquine (97 microM) inhibited PGI2 synthesis in both tissues. 2. Niridazole-induced inhibition in the myometrium was not reversed by exogenous arachidonic acid (33 microM) indicating a direct effect of the compound on PGI2 synthesizing enzymes. 3. Chloroquine-induced inhibition in the myometrium was significantly reversed by exogenous arachidonic acid (33 microM) indicating a direct effect of the compound on arachidonic acid releasing enzymes (e.g. phospholipases A2 and C). 4. Niridazole and chloroquine also inhibited prostaglandin E2 synthesis in the myometrium. 5. Chloroquine- and niridazole-induced inhibition of prostaglandin synthesis may contribute towards a better understanding of some of their actions in vivo.