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PubMed1985

Estradiol benzoate decreases nigral GABAergic activity in male rats.

Repeated doses of estradiol benzoate (10 micrograms/kg, s.c., once a day for 2, 5 or 8 days) to male rats decreased gamma-aminobutyric acid (GABA) content and glutamate decarboxylase (GAD) activity in substantia nigra (SN) but failed to change these parameters in hippocampus, cerebral cortex, cerebellum, lateral septum and olfactory tubercle. In the caudate nucleus, estradiol benzoate decreased GABA concentration but did not modify GAD activity. A decrease in nigral GABA concentration and GAD activity was also observed 24 and 48 but not 3 h after a single injection of estradiol benzoate. These data are consistent with results on GAD activity reported by McGinnis et al. in ovariectomized rats. Kinetic analysis of nigral GAD activity revealed that repeated estradiol benzoate injection reduced the Vmax without affecting the Km of GAD. Estradiol benzoate also reduced the rate of nigral GABA accumulation resulting from local infusion of gabaculine, suggesting that the steroid decreases GABA turnover in male rat SN. Hypophysectomy decreased GABA content and GAD activity in SN and GABA content in striatum. Administration of estradiol benzoate for 8 days to hypophysectomized rats failed to decrease further these parameters. Taken together, these data suggest that estradiol benzoate decreases SN GABAergic activity and that the integrity of the pituitary gland is required for this effect.

Animals↗
PubMed1994

Generation of hexahydrophthalic anhydride atmospheres in a controlled human-use test chamber.

A method for generating controlled atmospheres of hexahydrophthalic anhydride (HHPA) in an 8 m3 exposure chamber was developed. The permeation principle was used for gaseous HHPA generation. HHPA concentration was monitored by sampling on XAD-2 tubes and by a Fourier-transform infrared (FTIR) spectrometer using the partial least-square quantitative method. The repeatability of the FTIR was 5%, the reproducibility 12%, and the limit of detection 10 micrograms/m3. A bubbler method determined the sum of HHPA and HHP acid by using gas chromatography/mass spectrometry detection after derivatization with methanol/boron trifluoride. The precision of the work-up procedure was 3% and the recovery was 94% at 300 ng sampled amount of HHPA. The limit of detection was 10 ng HHPA. The variation in the permeation rate was 3% over 3 days. Different concentrations in the exposure chamber were generated by changing the temperature of the permeation tubes. The generated HHPA concentration range, at human exposure, was 3-90 micrograms/m3. The concentration at one temperature was reproducible even after major changes in the temperature. The coefficient of variation (CV) of six samples from different places in the breathing zone was 3%. The variation in the concentration, during an 8-hour human exposure at 10 micrograms/m3, was 3%. Time-weighted averages (8 hour) for human exposures of 10 micrograms/m3 (CV = 15%; n = 6); 37 micrograms/m3 (CV = 5%; n = 5); and 81 micrograms/m3 (CV = 6%; n = 9) were obtained at intended concentrations of 10 micrograms/m3, 40 micrograms/m3, and 80 micrograms/m3. The loss of HHPA in the exposure chamber was 54% (CV = 17%).(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants↗
PubMed2001

Behavioral effects of agents active at the gamma-aminobutyric acid receptor complex in the staircase paradigm.

This study examined the behavioral effects of agents active at the gamma-aminobutyric acid (GABA(A)) receptor complex in the mouse staircase paradigm. The neuroactivesteroids dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) were compared with the benzodiazepine agonist clonazepam, the non-benzodiazepine hypnotic compound zopiclone, and the antiepileptic agent gabapentin. Clonazepam, zopiclone and gabapentin reduced rearing activity at doses that did not affect climbing. The rearing-suppression effect of clonazepam and zopiclone, but not of gabapentin, was blocked by the benzodiazepine antagonist flumazenil, suggesting that the added effect of gabapentin is not mediated by the benzodiazepine receptor on the GABA complex. DHEA suppressed rearing behavior at doses that did not reduce climbing, but analysis with the Bonferroni post hoc test yielded no statistically significant difference. This inhibitory effect was attenuated by flumazenil. By contrast, DHEA-S suppressed, in a dose-dependent manner, both rearing and climbing behavior to the same extent. The findings support the potential value of the mouse staircase paradigm for demonstrating behaviorally relevant anxiolysis of test compounds shown to interact in vitro with the GABA(A) receptor complex.

Acetates↗
PubMed1991

Intestinal absorption of gabapentin in rats.

Gabapentin (1-aminomethyl-)cyclohexaneacetic acid, Gö 3450, CI-945; CAS 60142-96-3) is a new gamma-aminobutyric acid (GABA) analogous compound that has shown an anticonvulsive effect as well as low toxicity in preclinical and clinical studies. The substance is well absorbed after oral administration and penetrates the blood-brain barrier. The aim of experiments was to study the mechanism of intestinal absorption, the relationship between the absorption rate and the applied concentration and whether the absorption rate differs between different parts of the intestine. For this purpose, isolated intestinal segments of rats (everted sac preparations) were used. Due to the fact that gabapentin is not metabolized in the intestine, its concentration in the mucosal and serosal compartments could be determined by scintillation counting of 3H-gabapentin. The results showed that gabapentin was absorbed by simple diffusion because neither indications for an uphill nor for a carrier-mediated transport could be demonstrated. The absorption rate was linearly related in the concentration range from 0.001 to 100 mmol/l. There was no significant difference between the absorption rate in the three parts of the small intestine at 1 and 10 mmol/l, while the absorption rate was significantly (p less than 0.01) lower in the colon.

Acetates↗
PubMed1979

Effect of p-hydroxyphenyl-propionic ester of tranexamic acid hydrochloride (Cetraxate) on peptic ulcer. Multi-center clinical study.

The therapeutic effects of a new antiulcer drug, a p-hydroxyphenyl-propionic ester of tranexamic acid (cetraxate, CET) hydrochloride, were investigated in 234 patients with gastric ulcer by double blind controlled study using trans-3,7-dimethyl-2,6-octadienyl-5,9,13-trimethyltetradeca-4,8,12-trienoate (gefarnate) as the standard drug in 18 medical institutions. The cure rates confirmed by endoscopic examination in CET-treated patients were 28, 61 and 73% each after 4, 8 and 12 weeks of medication, while those in gefarnate-treated patients were 23, 47 and 55%, respectively, with statistical significance after 8 and 12 weeks. Global utility rate based on the judgement by the physician in charge also supported the results with cure rate. Stratified analysis again confirmed the superiority of CET hydrochloride against gefarnate in the hospitalized patients in terms of both cure rate and global utility rate. However, there was no significant difference between the two drugs as to the effects in the out-patients. Among the symptoms, there was also a significant difference between the improvement rate of epigastralgia with the two drugs in favour of CET hydrochloride. No serious side effects were reported throughout the study.

Adolescent↗
PubMedDate not supplied

Methods for the identification of chemical respiratory allergens in rodents: comparisons of cytokine profiling with induced changes in serum IgE.

No validated or widely recognized test methods are currently available for the prospective identification of chemicals with the potential to cause respiratory allergy. The cellular and molecular mechanisms that result in the induction of chemical sensitization of the respiratory tract are unclear, although there is evidence for the selective development of T helper 2 (Th2)-type responses and, in some cases, the production of IgE antibody. We have therefore examined the utility of cytokine profiling using BALB/c mice, together with the measurement of induced increases in the total serum concentration of IgE in the Brown Norway (BN) rat, as markers for the prospective identification of chemical respiratory allergens. Responses provoked by the reference respiratory allergen trimellitic anhydride (TMA) have been compared with those stimulated by the respiratory sensitizing diisocyanates toluene diisocyanate (TDI) and hexamethylene diisocyanate (HDI) and by the acid anhydride hexahydrophthalic anhydride (HHPA). Topical exposure of BN rats to TMA, TDI and HHPA each provoked marked immune activation (increases in lymph node cellularity and proliferation). However, only treatment with TMA stimulated vigorous increases in the total serum concentration of IgE. In contrast, exposure to HHPA, TDI or HDI failed to provoke significant changes in serum IgE concentration or induced only transient and relatively weak increases in serum IgE levels. In parallel experiments using BALB/c strain mice, however, topical application of all four chemical respiratory allergens provoked a marked Th2-type cytokine secretion profile in draining lymph node cells. These data suggest that the measurement of induced changes in serum IgE is not sufficiently sensitive for the robust identification of chemical respiratory allergens. Furthermore, irrespective of the reasons for variations in TMA-induced IgE production among BN rats, doubts remain regarding the utility of these animals for the characterization of immune responses to chemical allergens. Cytokine profiling using the BALB/c strain mouse apparently provides a more robust method for the hazard assessment of chemical respiratory allergens.

Administration, Topical↗
PubMedDate not supplied

Brain microdialysis and PK/PD correlation of pregabalin in rats.

Pregabalin [PGB, (S)-3-isobutyl GABA, CI-1008] is a derivative of the inhibitory neurotransmitter g-aminobutyric acid (GABA). It has shown anticonvulsant, analgesia and anxiety activity in animal models. In this report, blood-brain barrier (BBB) influx and efflux of PGB were investigated with microdialysis at efficacious doses in rats. BBB influx (CLin) and efflux (CLout) permeability for pregabalin were 4.8 and 37.2 microL/min/g brain, respectively, following an intravenous infusion to rats. The results indicate that PGB is brain penetrable, supporting its anti-epilepsy and other CNS pharmacology. Significant anticonvulsant action of PGB was detected between 2 and 8 hr post oral dose, which is lag behind ECF drug concentrations lees. A PK/PD link model was used to describe the counter-clockwise hysteresis relationship between pregabalin brain ECF concentration and the anticonvulsant effect in rats. The resulting Ce (concentration in effect compartment) versus effect profile exhibits a sigmoidal curve and the calculated ECe50 and Keo values were 95.3 ng/mL and 0.0092 min-1, respectively. The small Keo value suggests that the effect is not directly proportional to the amount of pregabalin in the ECF compartment possibly due to inherent delay.

Acetates↗
PubMed2004

Gabapentin maintenance decreases smoked cocaine-related subjective effects, but not self-administration by humans.

Data from research with laboratory animals indicate that cocaine self-administration can be reduced by lambda-aminobutyric acid (GABA) agonists. Yet, the effectiveness of GABA agonists to decrease human cocaine self-administration has not been investigated under controlled laboratory conditions. The purpose of this study was to assess the effects of gabapentin, a GABA agonist, on cocaine-related behaviors, including self-administration, in human research participants under controlled laboratory conditions. During this 48-day double-blind, crossover design study, the effects of gabapentin (0, 600, and 1200 mg/d) maintenance on response to cocaine (0, 12, 25, and 50 mg) were investigated in seven cocaine abusers. Active cocaine significantly increased choice to self-administer cocaine, subjective-effect ratings (e.g., "Good Drug Effect"), blood pressure and heart rate (HR). Gabapentin did not reduce cocaine choice or cardiovascular measures, but it did decrease some subjective effects of cocaine (e.g., "Good Drug Effect" and "Anxious"). These data suggest that the cocaine-gabapentin combination was well-tolerated, and because some cocaine-related subjective effects were reduced by maintenance on relatively low gabapentin doses, future studies should test higher gabapentin doses.

Acetates↗
PubMed1983

Possible involvement of humoral regulation in the effects of elevated cerebral 4-aminobutyric acid levels on the polyamine metabolism in brain.

It has been reported in several recent studies that the manipulation of cerebral 4-aminobutyric acid (GABA) level results in unexpected changes in the cerebral polyamine metabolism in vivo. The mechanisms behind these interactions have remained unknown. The present results show that the changes in polyamine metabolism are not limited to the brain, but are observable also in the liver, which served as a peripheral reference tissue. Different types of responses in the activities of the polyamine-synthesizing enzymes, ornithine decarboxylase and adenosylmethionine decarboxylase, were observed after increasing the cerebral GABA concentration of mice with varying doses of two GABA transaminase inhibitors, gabaculine and ethanolamine-O-sulphate. The time course of the significant changes in the enzyme activities showed significant correlation between the brain and liver. The possibility of direct effects of the drugs on liver was excluded by injecting them intracerebroventricularly, and by performing control experiments with equal doses given peripherally. It is concluded that the observed changes in the polyamine metabolism of liver are produced through centrally mediated humoral regulation, and that the corresponding changes in the brain are obviously due to the same factor or factors, since they are significantly correlated to the changes in liver.

4-Aminobutyrate Transaminase↗
PubMed2004

XP13512 [(+/-)-1-([(alpha-isobutanoyloxyethoxy)carbonyl] aminomethyl)-1-cyclohexane acetic acid], a novel gabapentin prodrug: II. Improved oral bioavailability, dose proportionality, and colonic absorption compared with gabapentin in rats and monkeys.

The absorption of gabapentin (Neurontin) is dose-dependent and variable between patients. Rapid clearance of the drug necessitates dosing three or more times per day to maintain therapeutic levels. These deficiencies appear to result from the low capacity, limited intestinal distribution, and variable expression of the solute transporter responsible for gabapentin absorption. Saturation of this transporter at doses used clinically leads to unpredictable drug exposure and potentially ineffective therapy in some patients. XP13512 [(+/-)-1-([(alpha-isobutanoyloxyethoxy)carbonyl]aminomethyl)-1-cyclohexane acetic acid] is a novel prodrug of gabapentin designed to be absorbed by high-capacity nutrient transporters located throughout the intestine. XP13512 was efficiently absorbed and rapidly converted to gabapentin after oral dosing in rats and monkeys. Exposure to gabapentin was proportional to prodrug dose, whereas exposure to intact XP13512 was low. In rats, >95% of an oral dose of (14)C-XP13512 was excreted in urine in 24 h as gabapentin. In monkeys, oral bioavailability of gabapentin from XP13512 capsules was 84.2% compared with 25.4% after a similar oral Neurontin dose. Compared with intracolonic gabapentin, intracolonic XP13512 gave a 17-fold higher gabapentin exposure in rats and 34-fold higher in monkeys. XP13512 may therefore be incorporated into a sustained release formulation to provide extended gabapentin exposure. XP13512 demonstrated improved gabapentin bioavailability, increased dose proportionality, and enhanced colonic absorption. In clinical use, XP13512 may improve the treatment of neuropathic pain, epilepsy, and numerous other conditions by increasing efficacy, reducing interpatient variability, and decreasing frequency of dosing.

Administration, Oral↗
PubMed1996

[New medical treatment of epilepsy].

Nearly three-fourths of all newly diagnosed cases of epilepsy are easily controlled with our current drug armamentarium. Further progress will undoubtedly come with use of three new drugs, gabapentin, lamotrigine, and vigabatrin now in diverse stages of clinical trials. Gabapentin is a gamma-aminobutyric acid (GABA) analog which passes the blood-brain barrier. Its mode of action is unknown. The anti-convultion effect of lamotrigine apparently results from its capacity to stabilize voltage-dependent sodium channels and thus limit release of the excitory neuromediator glutamate. Vigabatrin produces irreversible inhibition of GABA transaminase, increasing the concentration of this neurotransmittor inhibitor in the brain. The pharmacokinetic properties of these three anti-epileptics are more favorable than those of earlier drugs. Renal excretion is proportional to creatinine clearance allowing better dose adjustment and all three can be associated with oral contraception. They are as effective as the classical agents although indications may vary. There are fewer adverse effects and no teratogenic effect has been observed in animal studies. Clinical surveillance is usually sufficient without laboratory tests. One handicap is the increased cost although it has been demonstrated that the overall cost for the society for a patient with well controlled epilepsy is less. The prescription of a third-generation anti-epileptic drug is justified immediately whenever treatment with one of the classical drugs has been unsuccessful; however, in case of failure the new drug should not be continued.

Acetates↗
PubMed1996

Spectral properties of environmentally sensitive probes associated with horseradish peroxidase.

The environmentally sensitive fluorescent probes 6-propionyl-2-(N,N-dimethylamino)naphthalene (PRODAN) and 2'-(N,N-dimethylamino)-6-naphthoyl-4-trans-cyclohexanioc acid (DANCA) form complexes with the heme binding site of apohorseradish peroxidase. The dissociation constants of the PRODAN and DANCA complexes were determined from anisotropy titration data to be approximately 8.7 x 10(-5) and 3.3 x 10(-4) M, respectively. From comparison of the steady state fluorescence spectra of PRODAN and DANCA in solvents of varying dielectric constants, and in the apohorseradish peroxidase complex, we conclude that the heme binding site of horseradish peroxidase is relatively polar. The lifetimes of PRODAN and DANCA in organic solvents of varying polarities can be fit to single exponential decays. However, the lifetimes of PRODAN and DANCA associated with apohorseradish peroxidase, determined using a background subtraction method to correct for the non-negligible fluorescence of unbound probe, fit best to a distribution of lifetime values. We attribute these lifetime distributions to microenvironmental heterogeneity which is also consistent with the observed dependence of the emission maxima of PRODAN-apohorseradish peroxidase upon the excitation wavelength. In neither the PRODAN nor the DANCA case was evidence found in the time-resolved data for relaxation of the protein matrix around the excited state probe dipole.

2-Naphthylamine↗
PubMed1980

Activation of factor XII in plasma from rats pretreated with tranexamic acid. Inhibition of a plasmin-induced loss of the functional activity of high molecular weight kininogen.

Incubation of plasma from rats pretreated with tranexamic acid (40 mg/100 g) with acetone (23% V/V) yielded enzyme preparations in which all the plasminogen present was recovered as plasmin and a plasmin-like substance without affinity for lysine-Sepharose. This substance, designated "plasmin", was separated from plasmin and kallikrein in a three-step procedure using columns of lysine-Sepharose, DEAE-Sephadex A-50, and arginine-Sepharose. The ratios of fibrinolytic, caseinolytic, LEe esterase, BAEe esterase and kininogenase activities of "plasmin" corresponded well with those of rat plasmin and human plasmin. Both rat plasmin and "plasmin" destroyed the capacity of high molecular weight kininogen (HMWK) to function as a cofactor in the activation of factor XII in rat plasma, without causing a corresponding release of the kinin part of the molecule. Rat plasma kallikrein induced full release of kinin from HMWK, but the functional capacity was retained. It is suggested that the reduced extent of activation of factor XII observed in plasma from rats injected intravenously with dextran, or rat plasma that has been passed through a column with lysine-Sepharose, is due to the loss of functional HMWK caused by plasmin activated in vivo or on the column.

Animals↗
PubMed1991

Comparison of gabapentin with other antiepileptic and GABAergic drugs.

The effect of the experimental antiepileptic drug gabapentin (1-(aminomethyl) cyclohexane acetic acid; GPT) on the feline trigeminal complex was compared with the effect of established antiepileptic drugs and with the effect of GABAA and GABAB agonists and antagonists. Intravenous injection of 10-60 mg/kg GPT depressed the descending periventricular facilitation of trigeminal nucleus neurons, as well as segmental excitatory mechanisms. On the other hand, GPT usually facilitated, but sometimes depressed, both segmental and periventricular inhibitory mechanisms. GPT thus resembled carbamazepine and phenytoin in its action on excitatory mechanisms and on segmental inhibition, but differed in its effect on inhibitory pathways descending from the reticular formation. In agreement with our observations, GPT has been found to be effective against partial and generalized tonic-clonic seizures, similar to the spectrum of activity of carbamazepine and phenytoin. The action of GPT in our model also resembled that of the GABAB agonist baclofen in its facilitation of reticular and segmental inhibitory mechanisms and its depression of segmental excitatory mechanisms, but differed in its effect on excitatory mechanisms descending from the reticular formation. GPT has also been reported to mimic GABAB receptor activation in other experiments but appeared to act by a GABA-receptor independent mechanism.

Acetates↗
PubMed2002

Effects of the phosphodiesterase 4 inhibitors SB 207499 and AWD 12-281 on the inflammatory reaction in a model of allergic dermatitis.

The inhibitors of the phosphodiesterase 4, SB 207499 (cilomilast, c-4-cyano-4-(3-cyclopentyloxy-4-methoxy-phenyl)-r-L-cyclohexane carboxylic acid) and AWD 12-281 (N-(3,5-dichloropyrid-4-yl)-[1-(4-fluorobenzyl)-5-hydroxy-indole-3-yl]-glyoxylic acid amide) were tested in a model of allergic dermatitis in mice. To obtain an allergic dermatitis, BALB/c mice were sensitized to toluene-2,4-diisocyanate. The allergic reaction was challenged by topical administration of toluene-2,4-diisocyanate onto the mice ears. Before challenge, two groups of mice were treated topically (ear skin) with SB 207499 or AWD 12-281. There was a significant ear swelling in toluene-2,4-diisocyanate-challenged mice ears 4, 8, 16, 24 and 48 h after challenge. SB 207499 and AWD 12-281 inhibited this swelling significantly 8, 16, 24 and 48 h after the challenge. For biochemical parameters and histology, ears were sampled from mice sacrificed 4, 8 and 16 h after the challenge. In homogenized tissue, SB 207499 and AWD 12-281 inhibited significantly the secretion of interleukin 1beta induced by toluene-2,4-diisocyanate 4 and 8 h after challenge. The cell influx (granulocytes) observed in the toluene-2,4-diisocyanate-challenged mice 8 and 16 h after challenge was nearly abolished by AWD 12-281 and SB 204799.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

Gabapentin potentiates the conductance increase induced by nipecotic acid in CA1 pyramidal neurons in vitro.

The anticonvulsant gabapentin (1-(aminomethyl)cyclohexane acetic acid) has been found to be effective for treatment of partial seizures, but the mechanism of action is unknown. Recent evidence from the rat optic nerve suggests that gabapentin may enhance promoted release of GABA, which is thought to be due to reverse operation of the GABA transporter. We have used whole-cell patch clamp recordings from CA1 pyramidal neurons in hippocampal slices to directly measure currents induced by nipecotic acid (NPA) during exposure to gabapentin. Under control conditions, pressure microejection of NPA increased whole-cell conductance with a reversal potential equal to the chloride equilibrium potential. This response was mimicked by GABA application, and blocked by bicuculline. The response to NPA was also present after blockade of synaptic transmission in the presence of calcium-free solution. These results are consistent with NPA promoting nonvesicular release of GABA from neighboring neurons or glia via reverse operation of the GABA uptake system, which then activated GABAA receptors on the recorded neurons. In control solution, the response to NPA slowly decreased over 45 min to approximately 50% of the initial response, consistent with GABAA receptor 'rundown'. However, in the presence of gabapentin there was a slow increase in the response, reaching approximately 170% of the control level after 45 min of gabapentin exposure. These results demonstrate that gabapentin enhances the promoted release of GABA by more than three-fold. The potentiation of the NPA response may be due to gabapentin increasing cytosolic GABA in neighboring cells via a delayed metabolic effect, and would have the functional effect of increasing neuronal inhibition during periods of hyperexcitability.

Acetates↗
PubMed1983

Comparison between antifibrinolytic and antiprostaglandin treatment in the reduction of increased menstrual blood loss in women with intrauterine contraceptive devices.

The effects of a fibrinolysis inhibitor (tranexamic acid, TA) and prostaglandin synthesis inhibitor (diclofenac sodium, DS) were compared in the reduction of excessive menstrual blood loss in 19 women with an intrauterine contraceptive device (IUCD). These women (mean blood loss before treatment to 135.1 +/- 18.9 SE ml, range 70-294 ml) were treated in random order with TA (1.5 g three times daily for 5 days starting on the first day of menstruation for two periods), and with DS (50 mg three times on the first day followed by 25 mg three times daily for 4 days, for two periods), or with placebo (one period) in a double-blind trial. The placebo treatment did not change menstrual blood loss (128.3 +/- 15.6 ml). The TA treatment decreased blood loss to 59.4 +/- 7.7 ml (P less than 0.001) and the DS treatment to 102.1 +/- 13.6 ml (P less than 0.01). Neither treatment abolished pelvic discomfort during menstruation or shortened its duration. Various side-effects were noted by 12 women during 19 TA treatments and by five women during six DS treatments. Thus, while TA is generally far more effective, DS gave pronounced decreases in menstrual bleeding in some women and had less frequent side-effects.

Adult↗
PubMed1985

Inhibition of delayed hypersensitivity reactions by a new agent, cis-1-methyl-4-isohexylcyclohexane carboxylic acid (IG-10).

A newly synthesized compound, cis-1-methyl-4-isohexylcyclohexane carboxylic acid (IG-10), has been reported as an inhibitor of delayed hypersensitivity reaction. In the present paper, the mechanisms regarding the inhibitory action of IG-10 was investigated on delayed hypersensitivity reactions. p-Phenylenediamine-induced contact dermatitis in guinea pigs was significantly inhibited when the drug was given in a dose of 100 mg/kg p.o. at various times after challenge with the antigen. IG-10 inhibited both contact dermatitis and monocytes or neutrophils infiltrations induced by picryl chloride in mice. A skin reaction, similar to that seen in the case of delayed hypersensitivity reaction, was induced by an intradermal injection of phytohemagglutinin-P (PHA-P) stimulated lymphocytes in guinea pigs. This reaction was a useful method for assessing the effect of drugs on the release of lymphokines, particularly skin reactive factor (SRF). IG-10 in a concentration of 10(-5) g/ml inhibited the release of SRF as well as the release of migration inhibitory factor (MIF) from guinea pig lymphocytes stimulated by PHA-P. The reduction of delta 4-3-ketone of aldosterone and/or hydrocortisone by rat liver homogenates was not affected with IG-10, unlike that seen in the case of glycyrrhizin.

Aldosterone↗