dinoprost and Seizures

It is still an urgent need to find alternative and effective therapies to combat epileptic seizures. Tacrolimus as a potent immunosuppressant and calcineurin inhibitor is emerging as promising drug to suppress seizures. However, there are few reports applying tacrolimus to epilepsy and providing data for its antiseizure properties. In this study, we investigated the antiseizure effects of 5 and 10 mg/kg doses of tacrolimus treatment priorly to pentylenetetrazol (PTZ) induction of seizures in rats. As an experimental design, we establish two independent rat groups where we observe convulsive seizures following 70 mg/kg PTZ and sub-convulsive seizures detected by electroencephalography (EEG) following 35 mg/kg PTZ. Thereafter, we proceed with biochemical analyses of the brain including assessment of malondialdehyde level as an indicator of lipid peroxidation and detection of superoxide dismutase (SOD) enzyme activity and PGF2α. Tacrolimus pre-treatment dose-dependently resulted in lesser seizure severity according to Racine's scale, delayed start-up latency of the first myoclonic jerk and attenuated the spike percentages detected by EEG in seizure-induced rats. However, only the higher dose of tacrolimus was effective to restore lipid peroxidation. An increase in SOD activity was observed in the PTZ group, mediated by seizure activity per se, however, it was greater in the groups that received treatment with 5 and 10 mg/kg of Tacrolimus. PGF2α bursts following PTZ induction of seizures were reversed by tacrolimus pre-treatment in a dose-dependent manner as well. We report that the well-known immunosuppressant tacrolimus is a promising agent to suppress seizures. Comparative studies are necessary to determine the possible utilization of tacrolimus in clinical cases.

Topics: Animals; Anticonvulsants; Brain; Dinoprost; Disease Models, Animal; Epilepsy; Humans; Immunosuppressive Agents; Oxidative Stress; Pentylenetetrazole; Rats; Seizures; Superoxide Dismutase; Tacrolimus; Time-to-Treatment

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) that is commonly used as an anti-inflammatory, anti-pyretic, and analgesic. Although some studies have focused on the anti-inflammatory and anti-pyretic properties of ibuprofen during febrile convulsions, only one has investigated its antiepileptic effects. In the present study, we aimed to investigate the effects of ibuprofen in rats exposed to pentylenetetrazol (PTZ)-induced seizures. In total, 48 rats were randomly divided in two groups: Group A for electroencephalography (EEG) recordings and Group B for behavioral assessment. All EEG recordings and behavioral assessment protocols were performed. In addition, groups were compared in terms of prostaglandin F2 alfa (PGF2α) levels in the brain. We demonstrated the beneficial effects of the administration of ibuprofen in PTZ-induced seizures in rats via the following findings: spike percentages and Racine convulsion scale values were significantly lower and first myoclonic jerk (FMJ) onset times were significantly higher in the ibuprofen-administered groups. Moreover, PGF2α levels in the brain were significantly higher in the saline and PTZ 70 mg/kg group than in the control and PTZ 70 mg/kg and 400 mg/kg ibuprofen groups. Our study is the first to demonstrate the beneficial effects of ibuprofen on seizures through behavioral, EEG, and PGF2α brain assessments. Ibuprofen can be used for epilepsy and febrile seizures safely and without inducing seizures. However, further experimental and clinical studies are needed to confirm our results.

Topics: Animals; Anticonvulsants; Dinoprost; Ibuprofen; Male; Myoclonus; Pentylenetetrazole; Rats, Sprague-Dawley; Seizures

The immature brain is prone to seizure; however, the mechanism underlying this vulnerability has not been clarified. Febrile seizure is common in young children, and the use of non-steroidal anti-inflammatory drugs for febrile seizure is not recommended. In previous studies, we established that prostaglandin (PG) F2α, a product of cyclooxygenase (COX), acts as an endogenous anticonvulsant in the adult mouse. Therefore, we assumed that COX-2 activity was involved with seizure susceptibility in early life. In the present study, immature mice (postnatal day 9) were far more prone to kainic acid (KA)-induced seizures than mature mice (after postnatal day 35). Seizure activity began later in immature mice, but was more severe and was unaffected by a potent COX inhibitor, indomethacin; in contrast, indomethacin aggravated seizure activity in mature mice. Immature mouse brains exhibited little basal COX-2 expression and little KA-induced COX-2 induction, while KA-induced COX-2 expression and PGF2α release were prominent in mature brains. During brain development, COX expression was increased and glycosylated in an age-dependent manner, which was necessary for COX enzyme activity. Intracisternal PGF2α administration also reduced KA-induced seizure activity and mortality. Taken together, low COX activity and the resulting deficiency of PGF2α may be an essential cause of increased seizure susceptibility in the immature brain.

Topics: Age Factors; Animals; Animals, Newborn; Brain; Cells, Cultured; Cyclooxygenase 2; Dinoprost; Disease Susceptibility; Glycosylation; Mice; Seizures; Up-Regulation

Prostaglandin (PG) F(2α) is one of the major prostanoids biosynthesized by cyclooxygenases (COXs) from arachidonic acid. Although it has been reported that there is a selective surge in PGF(2α) production in the hippocampus during kainic acid (KA)-induced seizure activity, the precise intra-hippocampal distribution of PGF(2α) has not been elucidated due to the paucity of effective histological techniques for detecting PGs in tissues. We investigated the tissue distribution of PGF(2α) in the rat hippocampus 30 min after KA injection by developing fixation and immunohistological-staining methods. To detect PGF(2α) directly on histological sections, we used systemic perfusion fixation with water-soluble carbodiimide fixative, followed by immersion of the brains in Zamboni's fixative. We then performed immunofluorescence staining with anti-PGF(2α) antibody, with negative control experiments used to confirm the staining specificity. Definitive immunolabeling for PGF(2α) was evident most markedly in pyramidal cells of the hippocampal cornu Ammonis (CA) 3 sector and neurons of the hilus in KA-treated rats. Immunolabeling for PGF(2α) was also evident in granule cells of the dentate gyrus. Double immunfluorescence staining revealed that PGF(2α)-immunopositive neurons expressed cytosolic phospholipases A(2), COX-2, and FP receptor. These results suggest that the major source of PGF(2α) production immediately after KA injection was neurons of the hippocampal CA3 sector, hilus and dentate gyrus. These neurons exert PGF(2α)-mediated functions via FP receptors in an autocrine/paracrine manner and may play pathophysiological roles in the acute phase (30 min) of excitotoxicity.

Topics: Animals; CA3 Region, Hippocampal; Convulsants; Dinoprost; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique; Immunohistochemistry; Kainic Acid; Male; Rats; Rats, Wistar; Receptors, Prostaglandin; Seizures; Staining and Labeling

COX-2 and prostaglandins (PGs) might play important roles in epilepsy. In kainic acid-induced seizures, the brain largely increases PGD(2), first from COX-1 and later COX-2-induced PGF(2alpha). Pre-treatment with COX-2 inhibitors such as indomethacin, nimesulide, and celecoxib is known to aggravate kainic acid (KA)-induced seizure activity. However it is not known whether the proconvulsant effect of those non-steroidal anti-inflammatory drugs (NSAIDs) is due to changes in endogenous prostaglandins (PGs), or what types of PGs are involved. The purpose of this study was to determine the effect of intracisternally administered PGs on KA-induced seizures aggravated by pre- or post-treatment with COX-2 inhibitors. Systemic KA injection (10 mg/kg i.p.) in mice evoked mild seizure activity within 15 min. PGs were administrated intracisternally 20 min prior to KA administration. COX inhibitors (indomethacin, nimesulide, and ketoprofen, 10 mg/kg i.p.) were injected 1 h before or 15 min after KA. An additional COX-2 inhibitor, celecoxib, was administered orally. Intracisternally administered PGF(2alpha) (700 ng), but not PGD(2) (700 ng) or PGE(2) (700 ng) completely alleviated KA-induced seizures potentiated by COX-2 inhibitors, and also reduced KA-induced hippocampal neuronal death aggravated by indomethacin. PGF(2alpha) alone did not affect KA-induced seizures. However, an FP receptor antagonist, AL 8810 (10 or 50 ng) which is an 11beta-fluoro analogue of PGF(2alpha) potentiated KA-induced seizure activity dose-dependently. In summary, pre- or post-treatment with COX-2 inhibitors aggravates KA-induced seizures, which suggests to change the endogenous PGF(2alpha). Seizure-induced PGF(2alpha) might act as an endogenous anticonvulsant through FP receptors.

Topics: Analysis of Variance; Animals; Cell Survival; Cyclooxygenase Inhibitors; Dinoprost; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Electroencephalography; Kainic Acid; Male; Mice; Mice, Inbred ICR; Receptors, Prostaglandin; Seizures

We investigated whether prostaglandins (PGs), proinflammatory mediators implicated in excitatory activity, are involved in Shigella-related seizures. Pretreatment with S. dysenteriae sonicate (2LD(50)) enhanced mice response to pentylenetetrazole-induced seizures, without increase of brain concentrations of PGE(2), PGD(2) or PGF(2alpha). Preinjection of NS-398, an inhibitor of cyclooxygenase-2, before treatment with Shigella sonicate, had no effect on seizures. The anticonvulsive PGD(2) increased after injection of 8 LD(50) of Shigella sonicate, which did not enhance seizures (32 pg/mg vs 26 pg/ml, p=0.0063). The findings indicate that PGs are not involved in the enhanced seizure response after exposure to Shigella. However, induction of PGD(2) may play an inhibitory role.

Topics: Animals; Chi-Square Distribution; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Enzyme-Linked Immunosorbent Assay; Lethal Dose 50; Male; Mice; Mice, Inbred ICR; Nitrobenzenes; Pentylenetetrazole; Prostaglandin D2; Prostaglandins; Seizures; Shigella dysenteriae; Sulfonamides

This study was undertaken to evaluate the role of brain PGD2 activity during PTZ induced seizures in rats. Potentiation of endogenous PGD2 activity caused an anti-convulsant effect. Thus, after PGD2 injection (5 microg/icv) the latency of generalized tonic clonic convulsions was prolonged. ZK 118.182, a stable analogue of PGD2, dose-dependently inhibited the incidence and the intensity of seizures when injected at doses of 1-100 ng/icv. But on the other hand, inhibition of PGD2 activity either by a D-type PG receptor antagonist (AH 6809; 50 ng/icv) or by a PGD synthase inhibitor (sodium selenite; 0.2 microg/icv) produced a proconvulsant effect by increasing the incidence and the intensity of the seizures. These findings indicate that endogenous PGD2 activity in the brain may have a specific inhibitory role for the initiation and propagation of PTZ induced seizures in rats.

Topics: Animals; Anticonvulsants; Cerebral Ventricles; Dinoprost; Epilepsy, Tonic-Clonic; Injections, Intraventricular; Male; Pentylenetetrazole; Prostaglandin Antagonists; Prostaglandin D2; Rats; Rats, Wistar; Seizures; Sodium Selenite; Xanthenes; Xanthones

In gerbils pentylenetetrazole- or handling-induced seizures were accompanied by cerebral formation of small amounts of cysteinyl-leukotrienes (LT) but large amounts of prostaglandin (PG) F2 alpha. By contrast, in rats injected with pentylenetetrazole or bicuculline very large amounts of PGF2 alpha but no cysteinyl-LT could be detected in the brain tissues. The data indicate that at least in rats the extensive neuronal activity during tonic-clonic convulsions is not necessarily sufficient for the activation of the 5-lipoxygenase pathway. Apparently important species differences do exist.

Topics: Animals; Bicuculline; Brain; Dinoprost; Epilepsy; Gerbillinae; Handling, Psychological; Kinetics; Pentylenetetrazole; Seizures; SRS-A

In rats kainic acid-induced seizures were accompanied by time-dependent cerebral cysteinyl-leukotriene (LT) and prostaglandin (PG) F2 alpha formation. Cysteinyl-LT were identified in the rat brain tissue extracts by their immunoreactive properties and their retention times upon reversed phase HPLC profiling. In perfused blood-free brain tissue contents of LTC4-like material were significantly elevated in cortex, hippocampus, midbrain and hypothalamus at 3 h after kainic acid injection. PGF2 alpha tissue contents were significantly elevated in all brain areas studied with very large amounts in the hippocampus and smaller amounts in the cortex. The cyclooxygenase inhibitor indomethacin significantly inhibited formation of PGF2 alpha in whole brain tissue while leaving unaffected the production of cysteinyl-LT. A dose of indomethacin which nearly completely inhibited cyclooxygenase activity as monitored by cerebral PGF2 alpha contents also tended to aggravate behavioral changes and significantly increased the mortality. Phenidone, a lipoxygenase inhibitor, significantly and dose-dependently inhibited formation of cysteinyl-LT but did not significantly affect PGF2 alpha formation. Seizure activity tended to be attenuated by a higher dose of this compound. Dexamethasone which supposedly inhibits phospholipase A2 activity by induction of lipocortins, did not significantly reduce either cysteinyl-LT or PGF2 alpha biosynthesis. Flunarizine, trifluoperazine and diazepines protected a certain percentage of animals from kainic acid-induced seizures. In rats in which seizures occurred in spite of pretreatment with these compounds, the eicosanoid formation was not inhibited but in the case of flunarizine was even found to be somewhat enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Brain; Dinoprost; Dose-Response Relationship, Drug; Eicosanoids; Enzyme Inhibitors; Indomethacin; Kainic Acid; Kindling, Neurologic; Male; Rats; Rats, Inbred Strains; Seizures; SRS-A

Tonic-clonic seizures elicited in convulsion-prone gerbils resulted in a large increase in immunoreactive prostaglandin (PG) F2 alpha and in a smaller increase in immunoreactive leukotriene (LT) C4-like material in brain tissue. Brain tissue contents of both eicosanoids were found to reach a maximum at 6 min after the onset of seizures and were still elevated at 54 min after the beginning of convulsions. By reversed phase HPLC the immunoreactive LTC4-like material was identified as LTC4 and LTD4 at 6 min after the onset of convulsions, whereas at 54 min after the onset, transformation of LTD4 to LTE4 could be detected as well. In gerbils showing only weak seizure activity a small increase in PGF2 alpha but no increase in immunoreactive LTC4-like material could be detected at 6 min after the onset of convulsions. Pretreatment with indomethacin abolished the formation of PGF2 alpha but significantly enhanced the biosynthesis of immunoreactive LTC4-like material at 18 min after the beginning of seizures. The results demonstrate formation of cysteinyl-LT following tonic-clonic convulsions in spontaneously convulsing gerbils which could be enhanced by inhibition of the cyclooxygenase pathway of arachidonic acid metabolism. Since cysteinyl-LT have potent biological actions in various organs this finding warrants further investigations on the potential role of cysteinyl-LT in the CNS.

Topics: Animals; Brain; Dinoprost; Female; Gerbillinae; Indomethacin; Kinetics; Leukotriene E4; Male; Prostaglandins F; Seizures; SRS-A

Prostaglandins (PGs) of the E series are known to exert anticonvulsant action in experimental animals. Earlier studies from this laboratory have indicated that PGE1 inhibits pentylenetetrazole (PTZ)-induced convulsions in rats through a serotonin-mediated mechanism. PGD2, the major PG in the rodent brain, shares a number of central pharmacological actions of the PGEs, and like the latter it potentiates the anticonvulsant action of phenobarbitone and phenytoin in rats. The present study was undertaken to investigate the putative anticonvulsant action of PGD2 against PTZ-induced convulsions in rats and to evaluate the role of serotonin in the anticonvulsant action of PGD2. PGD2 (5, 10, and 20 micrograms, icv) produced a dose-related inhibition of PTZ-induced clonic convulsions in rats. The anticonvulsant action of PGD2 (20 micrograms, icv) was significantly attenuated following pretreatment of the rats with pharmacologic agents known to reduce central serotonergic activity, including 5,6-dihydroxytryptamine, a selective neurotoxin for serotonergic neurons, p-chlorophenylalanine, a specific inhibitor of serotonin biosynthesis, metergoline, a serotonin postsynaptic receptor antagonist, and quipazine, which is known to inhibit neuronal release of serotonin. These findings, in conjunction with an earlier study from this laboratory indicating that PGD2 augments rat brain serotonergic activity, suggest that the anticonvulsant activity of PGD2 against PTZ-induced convulsions in rats is mediated through a serotonergic mechanism.

Topics: Animals; Dihydroxytryptamines; Dinoprost; Female; Fenclonine; Male; Metergoline; Pentylenetetrazole; Prostaglandin D2; Quipazine; Rats; Rats, Inbred Strains; Seizures; Serotonin

Enzymatic production of prostaglandins (PGs) from exogenous arachidonic acid was studied in brain microsomal fractions prepared from mice following pentylenetetrazol (PTZ)-induced convulsions. Prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) measured either by radioimmunoassay or after incubation with [1-14C]arachidonic acid (AA) was significantly increased in microsomes from the convulsed animals. Pretreatment of the mice with the anticonvulsant ethosuximide prevented the enhanced PG production. The increased PG synthesis could not be attributed to an increased substrate availability nor to an activated phospholipase nor to a direct effect of the convulsant on the fatty acid cyclooxygenase. Evidence that a modification of the cyclooxygenase had occurred with seizure activity was obtained from kinetic analysis; the apparent Km for the AA was lowered from 30 +/- 3 microM in the controls to 12 +/- 1 microM in the PTZ-treated mice. Further evidence for a modification of the fatty acid cyclooxygenase was obtained from incubations of the microsomes with catalase to reduce peroxide formation. Limiting peroxide levels did not decrease the microsomal cyclooxygenase activity in the PTZ-treated mice to control levels. Seizure activity induced by picrotoxin and strychnine also increased the microsomal capacity of the convulsed animals to synthesize PGs. The increased brain fatty acid cyclooxygenase activity may result from a biochemical modification of the enzyme induced by seizure activity.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Brain; Dinoprost; Dinoprostone; Ethosuximide; Female; Kinetics; Mice; Microsomes; Pentylenetetrazole; Picrotoxin; Prostaglandin-Endoperoxide Synthases; Prostaglandins E; Prostaglandins F; Seizures; Strychnine

In view of the recent finding that prostaglandin D2 is stereospecifically converted to 9 alpha, 11 beta-prostaglandin F2, an isomer of prostaglandin F2 alpha, a highly specific and sensitive radioimmunoassay for 9 alpha, 11 beta-prostaglandin F2 was developed and applied to determine the content of this prostaglandin in various rat tissues. Antisera against 9 alpha, 11 beta-prostaglandin F2 were raised in rabbits immunized with the bovine serum albumin conjugate, and [3H]9 alpha, 11 beta-prostaglandin F2 was enzymatically prepared from [3H]prostaglandin D2. The assay detected 9 alpha, 11 beta-prostaglandin F2 over the range of 20 pg to 1 ng, and the antiserum showed less than 0.04% cross-reaction with prostaglandin F2 alpha, prostaglandin F2 beta and 9 beta, 11 beta-prostaglandin F2. To avoid postmortem changes, tissues were frozen in liquid nitrogen immediately after removal. The basal level of 9 alpha, 11 beta-prostaglandin F2 was hardly detectable in various tissues of the rat examined, including spleen, lung, liver and brain; although it was found to be 0.31 +/- 0.06 ng/g wet weight in the small intestine. During convulsion induced by pentylenetetrazole, enormous amounts of prostaglandin D2 (ca. 180 ng/g wet weight) and prostaglandin F2 alpha (ca. 70 ng/g) were produced in the brain; however, 9 alpha, 11 beta-prostaglandin F2 was detected neither there nor in the blood. This result demonstrates that the conversion to 9 alpha, 11 beta-prostaglandin F2 is a minor pathway, if one at all, of prostaglandin D2 metabolism in the rat brain.

Topics: Animals; Chromatography, High Pressure Liquid; Dinoprost; Immune Sera; Male; Pentylenetetrazole; Prostaglandin D2; Prostaglandins D; Prostaglandins F; Radioimmunoassay; Rats; Rats, Inbred Strains; Seizures; Tissue Distribution

The distribution of the two major cyclooxygenase products prostaglandin D2 (PGD2) and prostaglandin F2 alpha (PGF2 alpha) in 7 different regions of the brain (medulla, cerebellum, hypothalamus, striatum, midbrain, hippocampus and cerebral cortex) was studied. Basal levels were highest in hypothalamus and cortex. Following convulsions elicited by environmental stress prostaglandin concentrations increased in all areas, with largest increases (10-20-fold) in hippocampus and cortex, reaching 70 ng/g PGD2 in hippocampus and 115 ng/g PGD2 in cortex. These results demonstrate that, during spontaneous seizures, there is a greater increase in prostanoid production in those areas involved in the convulsive process.

Topics: Animals; Brain; Dinoprost; Female; Gerbillinae; Male; Prostaglandin D2; Prostaglandins D; Prostaglandins F; Radioimmunoassay; Seizures; Stress, Physiological; Time Factors

Basal levels of 5 cerebral prostanoids (PGD2, PGF2 alpha, PGE2, 6-keto-PGF1 alpha and thromboxane/TX/B2) were measured radioimmunologically in normal and convulsion-prone gerbils. Significantly less PGD2,PGE2 and 6-keto-PGF1 alpha was found in the brain of seizure-sensitive animals. After treatment with indomethacin, which reduced the amount of brain cyclo-oxygenase products, also normal gerbils exhibited convulsions following environmental stress. The results are in accordance with the hypothesis that endogenous prostanoids play a role in the regulation of seizure susceptibility.

Topics: Alprostadil; Animals; Brain; Brain Chemistry; Dinoprost; Dinoprostone; Disease Susceptibility; Female; Gerbillinae; Male; Prostaglandin D2; Prostaglandin-Endoperoxide Synthases; Prostaglandins D; Prostaglandins E; Prostaglandins F; Seizures; Thromboxane B2

The experiments reported herein were designed to study the effects of prostaglandin F2 alpha (PGF2 alpha) and PGE1 on operant behavior and rectal temperature of rats. A solution containing PGF2 alpha or PGE1 was infused intracerebroventricularly into rats trained to press a lever for food reward on a fixed interval 75 second (FI 75 sec) schedule. PGF2 alpha (10, 100 or 1000 ng/min) had no effect on FI 75 sec operant behavior. Only the highest dose increased temperature. PGE1 (100 ng/min) had no effect, whereas higher doses (250 and 500 ng/min) produced a rate-dependent effect on behavior, increasing low rates and decreasing high rates. The two higher doses also produced convulsions after about 25 min or 20 min infusions, respectively. PGE1 also increased temperature in a dose-dependent manner. Systemic administration of a low dose of d-amphetamine (0.5 mg/kg IP) had little or no effect on behavior or temperature. d-Amphetamine did not alter hyperthermia induced by the highest dose of PGF2 alpha, but antagonized the PGE1-induced hyperthermia. d-Amphetamine also antagonized all of the behavioral effects of PGE1, including convulsions. The results are discussed in relation to the actions of PGs and d-amphetamine on catecholamine neurons in the central nervous system.

Topics: Alprostadil; Animals; Behavior, Animal; Body Temperature; Catheterization; Conditioning, Operant; Dextroamphetamine; Dinoprost; Male; Prostaglandins E; Prostaglandins F; Rats; Reinforcement Schedule; Seizures

The present work examined some central nervous actions of prostaglandin D2 (PGD2), which is the most prevalent prostaglandin in rodent brain. The effects of PGD2 were compared with those of PGE2 and PGF2 alpha. The prostaglandins were administered intracerebroventricularly (ICV) to conscious rats using the method of Herman (1970). All three prostaglandins studied produced depressive behavioral effects, causing obvious sedation at doses of 2.0 micrograms and 20.0 micrograms ICV. PGD2 and PGE2 significantly reduced spontaneous motor activity at doses of 2.0 micrograms and 20.0 micrograms ICV. PGF2 alpha was less effective; only 20.0 micrograms significantly inhibited motor activity. At a dose of 20.0 micrograms ICV all three compounds were shown to block convulsions induced by pentylenetetrazol. PGD2, the most effective prostaglandin in this respect, was still slightly anticonvulsive at a dose of 2.0 micrograms ICV. PGF2 alpha hat the weakest anticonvulsive potency. PGE2 and PGF2 alpha (2.0 micrograms and 20.0 micrograms ICV) caused a marked hypertensive effect, whereas PGD2 at the same dose levels only produced a small increase in blood pressure. PGE2 and PGF2 alpha (2.0 micrograms and 20.0 micrograms) also exerted marked pyrogenic actions. The effects of PGD2 on body temperature were variable. When given at a dose of 20.0 micrograms ICV, it caused slight hyperthermia whereas a lower dose (2.0 micrograms ICV) induced a moderate fall in body temperature. These findings suggest a relationship between the actions of the different prostaglandins on blood pressure and body temperature.

Topics: Animals; Behavior, Animal; Blood Pressure; Body Temperature; Dinoprost; Dinoprostone; Injections, Intraventricular; Male; Motor Activity; Prostaglandin D2; Prostaglandins; Prostaglandins D; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains; Seizures

Prostaglandins are mainly used in clinical medicine for midterm abortion and to terminate pregnancy. Systemic adverse reactions include nausea and vomiting, which occur in approximately half of the patients and, to a lesser extent, diarrhea. Although bronchospasm occurs infrequently, PGF2 should be avoided in asthmatics. Cardiorespiratory failure culminating in prolonged coma and death has been reported. Moreover, convulsions and EEG changes have been observed in a comparatively small number of cases.

Topics: Abortifacient Agents; Abortion, Induced; Bronchial Spasm; Diarrhea; Dinoprost; Dinoprostone; Female; Heart Arrest; Humans; Pregnancy; Prostaglandins; Prostaglandins E; Prostaglandins E, Synthetic; Prostaglandins F; Seizures; Vomiting