ABSTRACT
A medicated plaster containing diclofenac epolamine (DHEP) and heparin has been recently proposed for the treatment of local trauma (ie, ankle sprains) accompanied by a clinically significant edema and/or hematoma formation, based on the combined antiinflammatory, hemorheologic, and antiedema properties of diclofenac and heparin. The aim of this study was therefore to compare the effects of a combined DHEP/heparin and DHEP alone in 2 clinical experimental models of microangiopathy, in order to provide a pharmacologic rationale for association of diclofenac and heparin. The microcirculation was evaluated by measuring cutaneous blood flow (laser Doppler) and transcutaneous oxygen and carbon dioxide pressures (TcPO(2) and TcPCO(2)) in 10 healthy volunteers before and after producing 2 microcirculatory models of microangiopathy: the models were based on reactive hyperemia (RH) and on local histamine injection, which both produce a significant increase in skin flux and alterations of TcPO(2) and TcPCO(2). The area of the study was the distal medial leg, treated with placebo, DHEP alone (Flector Tissugel), and DHEP/heparin (Flector Tissugel Heparin). The plasters were applied before producing the microcirculatory models to evaluate the efficacy of DHEP and DHEP/heparin in controlling and limiting vasodilatation and development of microangiopathy. A significant increase in cutaneous flux was obtained with both models. The application of DHEP partially limited the increase in flux and in TcPCO(2), as well as the decrease in TcPO(2) (which were considered signs of microangiopathy), but the combination DHEP/heparin was significantly more effective than DHEP alone. The inclusion of heparin in the plaster thus improved the control of the microcirculation achieved with diclofenac alone, when an experimental model of venous/arterial hyperemia and microangiopathy was used. In conclusion, DHEP in association with heparin modulates microcirculatory changes better than DHEP alone. It should be interesting to investigate the product in comparable clinical conditions in which it may be useful to act pharmacologically both on inflammation and microcirculatory disturbances that delay the recovery of patients.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anticoagulants/administration & dosage , Diclofenac/administration & dosage , Heparin/administration & dosage , Peripheral Vascular Diseases/drug therapy , Peripheral Vascular Diseases/physiopathology , Adult , Casts, Surgical , Drug Therapy, Combination , Female , Humans , Leg/blood supply , Male , Microcirculation/physiopathology , Middle Aged , Models, CardiovascularABSTRACT
G 619 is 3-carbamyl-(3'-picolyl)-4-methoxy-1-benzamide. The compound is structurally related to picotamide, a previously reported dual thromboxane synthase inhibitor/thromboxane A2 receptor antagonist, which displays inhibitory activity on tumor necrosis factor-alpha. The aim of the present work was to study the effect of G 619 on tumor necrosis factor-alpha synthesis both in vivo and in vitro. Salmonella enteritidis lipopolysaccharide was used to induce tumor necrosis factor-alpha production. Septic shock was produced in male rats by a single intravenous (i.v.) injection of 20 mg/kg (LD90) of Salmonella enteritidis lipopolysaccharide. Rats were pretreated with G 619 (50 mg/kg, i.v.) or vehicle (1 ml/kg, i.v.) 1 h before endotoxin challenge. Salmonella enteritidis lipopolysaccharide administration dramatically reduced survival rate (0%, 72 h after endotoxin administration), reduced mean arterial blood pressure, increased plasma levels of thromboxane B2 and 6-keto-prostaglandin F1 alpha and enhanced serum levels of tumor necrosis factor. Furthermore, endotoxic shock produced characteristic gastric damage, consisting of haemorrhagic infiltrates. Pretreatment with G 619 in vivo significantly protected against Salmonella enteritidis lipopolysaccharide-induced lethality (80% survival rate and 60% survival rate 24 h and 72 h after Salmonella enteritidis lipopolysaccharide injection, respectively), reduced hypotension, decreased plasma thromboxane B2 and serum tumor necrosis factor-alpha levels and enhanced blood levels of 6-keto-prostaglandin F1 alpha. In rat peritoneal macrophages, G 619 in vitro (25, 50 and 100 microM) significantly blunted (P < 0.001) Salmonella enteritidis lipopolysaccharide-stimulated production of tumor necrosis factor-alpha, whereas it increased 6-keto-prostaglandin F1 alpha and cyclic AMP levels. The present data indicate that G 619 may be useful during disease states characterized by elevated tumor necrosis factor-alpha levels.
Subject(s)
Benzamides/pharmacology , Picolines/pharmacology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , 6-Ketoprostaglandin F1 alpha/blood , Animals , Cyclic AMP/analysis , Gastric Mucosa/drug effects , Gastric Mucosa/pathology , Lipopolysaccharides , Macrophages, Peritoneal/drug effects , Male , Rats , Rats, Sprague-Dawley , Receptors, Thromboxane/antagonists & inhibitors , Salmonella enteritidis , Shock, Septic/chemically induced , Shock, Septic/prevention & control , Thromboxane B2/blood , Thromboxane-A Synthase/antagonists & inhibitors , Tumor Necrosis Factor-alpha/analysisABSTRACT
We investigated the effect of G 619, a dual thromboxane synthase inhibitor and thromboxane A2 (TxA2) receptor antagonist, in pentobarbital-anaesthetized rats subjected to left main coronary artery ligation (1 h) followed by reperfusion (1 h; MI/R). Sham-operated rats were used as controls (sham MI/R). Survival rate, myocardial necrosis, myocardial myeloperoxidase (MPO) activity (investigated as an index of leukocyte adhesion and accumulation) and serum creatine phosphokinase (CPK) activity were studied. MI/R injury significantly reduced survival rate (45%), caused a marked myocardial necrosis, increased serum CPK activity (sham MI/R = 35 +/- 12 U/ml; MI/R = 205 +/- 13 U/ml) and produced an increase in myocardial MPO activity in the area at risk and in the necrotic area (6.3 +/- 0.5 and 6.6 +/- 0.9 U x 10(-3)/g tissue, respectively). The administration of G 619 significantly increased survival rate, lowered the area of necrosis, blunted the increase in serum CPK activity and reduced the increase in MPO activity in both the area at risk and the necrotic area. These data are consistent with an involvement of TxA2 in MI/R injury and suggest that G 619 may represent a novel therapeutic approach to the treatment of acute myocardial infarction.
Subject(s)
Benzamides/pharmacology , Coronary Disease/therapy , Myocardial Reperfusion Injury/prevention & control , Neutrophils , Picolines/pharmacology , Receptors, Thromboxane/antagonists & inhibitors , Thromboxane-A Synthase/antagonists & inhibitors , Animals , Coronary Disease/enzymology , Creatine Kinase/blood , Disease Models, Animal , Leukocyte Count , Male , Myocardial Infarction/drug therapy , Myocardial Reperfusion Injury/enzymology , Neutrophils/metabolism , Peroxidase/metabolism , Rats , Rats, Sprague-Dawley , Survival Rate , Thromboxane A2/metabolismABSTRACT
Splanchnic artery occlusion (SAO) shock was induced in anesthetized rats by clamping the celiac trunk and the superior mesenteric artery for 45 min. The arteries were then released and survival rate, mean survival time, mean arterial blood pressure (MAP), plasma levels of thromboxane B2 (TxB2) and 6-keto-PGF1 alpha, and the phagocytotic activity of peritoneal macrophages were evaluated. Shocked animals died within 89 +/- 10 min, while all sham-shocked rats survived greater than 3 h. SAO shock produced relevant changes in MAP, significantly increased plasma levels of TxB2 and 6-keto-PFG1 alpha, and decreased peritoneal macrophage phagocytotic activity. The administration of G 619, a dual thromboxane synthase inhibitor/thromboxane A2 receptor antagonist (50 mg/kg, 15 min before SAO shock) significantly increased survival time (190 +/- 13 min) and survival rate, reduced plasma levels of TxB2, and partially restored the impairment in peritoneal macrophage phagocytosis. Finally, the administration of G 619 had beneficial effects on changes in MAP-induced bay SAO shock. These data further confirm the involvement of TxA2 in SAO shock and suggest that G 619 may have positive effects in low-flow states.
Subject(s)
Arterial Occlusive Diseases/complications , Benzamides/pharmacology , Picolines/pharmacology , Receptors, Prostaglandin/antagonists & inhibitors , Shock/prevention & control , Splanchnic Circulation/drug effects , Thromboxane-A Synthase/antagonists & inhibitors , 6-Ketoprostaglandin F1 alpha/pharmacology , Animals , Arterial Occlusive Diseases/physiopathology , Blood Pressure/drug effects , Macrophages/physiology , Male , Phagocytosis/drug effects , Radioimmunoassay , Rats , Rats, Inbred Strains , Receptors, Thromboxane , Shock/etiology , Shock/physiopathology , Thromboxane B2/bloodABSTRACT
The effect of oxiracetam on passive avoidance conditioned response and acetylcholine (ACh) levels in rats with selective lesions of the central monoaminergic pathways was investigated. The lesions were followed by a marked decrease in cortical serotonin (-88%), noradrenaline (-54%) and striatal dopamine (-57%) levels, while neither the performance of a passive avoidance conditioned response nor brain ACh levels were affected. Scopolamine (hyoscine) administration (0.63 mg/kg, s.c.) to lesioned rats exerted the expected amnesic effect, associated with a decrease in hippocampal, cortical and striatal ACh levels. In the rats with degeneration of dopaminergic and noradrenergic but not serotoninergic pathways, oxiracetam (50 and 100 mg/kg, s.c.) was unable to prevent both amnesia and the decrease in brain ACh levels caused by scopolamine. The effect of oxiracetam was prevented by haloperidol (0.2 mg/kg, s.c.). Our findings support the hypothesis that an interaction between monoaminergic and cholinergic neurotransmitter systems may be involved in the actions of nootropic drugs on cognitive functions.
Subject(s)
Acetylcholine/metabolism , Brain/metabolism , Catecholamines/metabolism , Memory/drug effects , Psychotropic Drugs/pharmacology , Pyrrolidines/pharmacology , Scopolamine/antagonists & inhibitors , Animals , Avoidance Learning/drug effects , Brain/drug effects , Cerebral Cortex/metabolism , Conditioning, Psychological , Corpus Striatum/metabolism , Dopamine/metabolism , Haloperidol/pharmacology , Hippocampus/metabolism , Male , Norepinephrine/metabolism , Rats , Rats, Inbred Strains , Serotonin/metabolism , Substantia Nigra/metabolismABSTRACT
The aim of this investigation was to compare the contact action of econazole sulfosalicylate (E-SSA) on mycetes (Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, Trichophyton rubrum, T. cutaneum, Pityrosporum sp.), Gram-positive bacteria (Staphylococcus aureus, Streptococcus faecalis) and Gram-negative bacteria (Escherichia coli, Citrobacter freundii) with that exerted by econazole nitrate (E-NIT). The results show E-SSA activity greater than E-NIT (in particular against mycetes and Gram-negative bacteria). The E-SSA contact activity trials illustrated certain properties of this imidazole sulfosolicylate such as: absence of latency time, antimicrobial activity proportional to its concentration, when a high concentration is used, given the limiting influence of pH and ionic strength of the medium. The higher E-SSA contact activity, in relation to E-NIT, can be correlated to its greater lipophylia considering also the lipophylic properties of SSA and the scarce dissociation of E-SSA.
Subject(s)
Econazole/analogs & derivatives , Econazole/pharmacology , Aspergillus fumigatus/drug effects , Candida albicans/drug effects , Cryptococcus neoformans/drug effects , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Microbial Sensitivity Tests , Mitosporic Fungi/drug effectsABSTRACT
The in-vitro activities of two new miconazole and econazole salts (sulfosalicylic acid formulation) against 98 clinical isolates of dermatophytes were evaluated, in comparison to those of miconazole, miconazole nitrate, econazole and econazole nitrate. Miconazole sulfosalicylate and econazole sulfosalicylate exhibited good activity towards all the dermatophytes tested, although econazole and its derivatives were more efficacious than miconazole and its salts. The new imidazoles were equally effective in inhibiting the fungal growth with respect to miconazole, miconazole nitrate, econazole and econazole nitrate.
Subject(s)
Antifungal Agents/pharmacology , Arthrodermataceae/drug effects , Miconazole/analogs & derivatives , Miconazole/pharmacology , Humans , Microbial Sensitivity TestsABSTRACT
Pyroglutamic acid (PCA) was compared with placebo in a randomized, double blind trial for assessing its efficacy in treating memory deficits in 40 aged subjects. Twenty subjects were treated with PCA and 20 with placebo over a period of 60 d. Memory functions were evaluated at baseline and after 60 d of treatment by means of a battery made up of 6 memory tasks. The results suggest that PCA is effective in improving some verbal memory functions in subjects affected by age-related memory decline.
Subject(s)
Memory Disorders/drug therapy , Pyrrolidinones/therapeutic use , Pyrrolidonecarboxylic Acid/therapeutic use , Aged , Aged, 80 and over , Double-Blind Method , Form Perception/drug effects , Humans , Memory Disorders/psychology , Middle Aged , Psychomotor Performance/drug effects , Randomized Controlled Trials as TopicABSTRACT
Intracerebroventricular administration (6 micrograms/2 microliters) of D-2-amino-5-phosphonovalerate (AP-5), a specific antagonist of the NMDA receptors, prior to training impaired the passive avoidance in a retention test in rat. Pretreatment with oxiracetam and D-pyroglutamic acid at doses ranging from 50 to 500 mg/kg SC dose-dependently prevented the disruptive effect of AP-5. This finding indicates that an interaction with excitatory amino acid NMDA type receptors may be important in behavioural effects of the two pyrrolidinone derivatives.
Subject(s)
Avoidance Learning/drug effects , Pyrrolidines/pharmacology , Pyrrolidinones/pharmacology , Pyrrolidonecarboxylic Acid/pharmacology , Receptors, Neurotransmitter/drug effects , Valine/analogs & derivatives , Animals , Injections, Intraventricular , Male , Motor Activity/drug effects , Rats , Rats, Inbred Strains , Receptors, N-Methyl-D-Aspartate , Valine/antagonists & inhibitors , Valine/pharmacologyABSTRACT
The two stereoisomers of pyroglutamic acid (PCA), a nootropic or cognition-enhancing agent, and classic reference compounds were investigated for their ability to interact with 27 neurotransmitter receptors and drug binding sites prepared from selected areas of the central nervous system and labelled with high affinity and selectivity with specific radioligands. L-PCA significantly interacted with the rat forebrain excitatory amino acid receptors labelled with 3H-L-glutamic acid. The IC50 of L-PCA was 28.11 microM, that of cold L-glutamic acid was 1.68 microM. The corresponding figure for L-aspartic acid was 16.95 microM. The indirect Hill plot gave coefficients of 0.48, 1.08 and 0.75 for L-PCA, L-glutamic and L-aspartic acids, respectively. Only very high concentrations (10(-4) M) of L-PCA were able to slightly antagonize the specific binding of 3H-clonidine to alpha 2-adrenergic receptors, of 3H-dihydroalprenolol to beta 1- and beta 2-adrenergic receptors of the heart and of the lung and of 3H-diazepam to benzodiazepine receptors. The D-isomer of PCA was practically as active as the L-isomer on these receptors. Finally, L-PCA (10(-5) to 10(-4) M) was unable to antagonize the specific binding of all the other radioligands to their respective receptors and binding sites. D-PCA did not significantly interact with excitatory amino acid receptors or with any of the other sites studied here.
Subject(s)
Pyrrolidinones/metabolism , Pyrrolidonecarboxylic Acid/metabolism , Animals , Binding Sites , Brain/metabolism , Calcium Channel Blockers/metabolism , Chloride Channels , Clonidine/antagonists & inhibitors , Diazepam/metabolism , Dose-Response Relationship, Drug , Glutamates/metabolism , Glutamic Acid , Guinea Pigs , Male , Membrane Proteins/metabolism , Mianserin/metabolism , Rats , Receptors, Adrenergic/metabolism , Receptors, Adrenergic, alpha/metabolism , Receptors, Adrenergic, beta/metabolism , Receptors, Amino Acid , Receptors, Cell Surface/metabolism , Receptors, Cholinergic/metabolism , Receptors, Dopamine/metabolism , Receptors, GABA-A/metabolism , Receptors, Glutamate , Receptors, Glycine , Receptors, Histamine/metabolism , Receptors, Muscarinic/metabolism , Receptors, Neurotransmitter/metabolism , Receptors, Opioid/metabolism , Receptors, Purinergic/metabolism , Receptors, Serotonin/metabolism , StereoisomerismABSTRACT
The effect of different doses of the cognition-enhancing agent oxiracetam on the disruption of acquisition of a passive avoidance conditioned response (step-through) by scopolamine 0.6 mg/kg s.c., and on the impairment of performance by scopolamine 0.2 mg/kg s.c. in an eight-arm maze was investigated in adult male Wistar rats. At the end of the experiments, ACh levels were measured in the cerebral cortex and hippocampus by an HPLC method, in order to ascertain whether a relationship exists between the effects of the two drugs on behavior and cholinergic function. In the step-through test, oxiracetam at doses of 50 and 100 mg/kg s. c., given 30 min. before scopolamine, antagonized both scopolamine-induced behavioral disruption and decrease in ACh levels but was inactive at the dose of 300 mg/kg s. c. In the eight-arm maze test, oxiracetam prevented scopolamine-induced disruption of the performance and decrease in brain ACh at the dose of 30 mg/kg s. c. but was inactive at the dose of 100 mg/kg s. c. In conclusion, when scopolamininduced disruption of behavior is prevented or reduced, the scopolamininduced decrease in ACh level, particularly in the hippocampus, is also reduced. The present results therefore offer further confirmation of a relationship between the cognition-enhancing effects of oxiracetam and its effects on hippocampal and cortical cholinergic mechanisms.
Subject(s)
Acetylcholine/metabolism , Brain Chemistry/drug effects , Cognition/drug effects , Psychotropic Drugs/pharmacology , Animals , Avoidance Learning/drug effects , Choline/metabolism , Male , Pyrrolidines/pharmacology , Rats , Rats, Inbred StrainsABSTRACT
1. This review has two aims: first, to marshal and discuss evidences demonstrating an interaction between nootropic drugs and brain cholinergic mechanisms; second, to define the relationship between the effects on cholinergic mechanisms and the cognitive process. 2. Direct or indirect evidences indicating an activation of cholinergic mechanisms exist for pyrrolidinone derivatives including piracetam, oxiracetam, aniracetam, pyroglutamic acid, tenilsetam and pramiracetam and for miscellaneous chemical structures such as vinpocetine, naloxone, ebiratide and phosphatidylserine. All these drugs prevent or revert scopolamine-induced disruption of several learning and memory paradigms in animal and man. 3. Some of the pyrrolidinone derivatives also prevent amnesia associated with inhibition of acetylcholine synthesis brought about by hemicholinium. Oxiracetam prevents the decrease in brain acetylcholine and amnesia caused by electroconvulsive shock. Oxiracetam, aniracetam and pyroglutamic acid prevent brain acetylcholine decrease and amnesia induced by scopolamine. Comparable bell-shaped dose-effect relationships result for both actions. Phosphatidylserine restores acetylcholine synthesis and conditioned responses in aging rats. 4. The mechanisms through which the action on cholinergic systems might take place, including stimulation of the high affinity choline uptake, are discussed. The information available are not yet sufficient to define at which steps of the cognitive process the action on cholinergic system plays a role and which are the influences of the changes in cholinergic function on other neurochemical mechanisms of learning and memory.
Subject(s)
Acetylcholine/metabolism , Brain/metabolism , Psychotropic Drugs/pharmacology , Animals , Brain/drug effects , Receptors, Cholinergic/drug effects , Receptors, Cholinergic/metabolism , Scopolamine/pharmacology , Synapses/drug effects , Synapses/physiologySubject(s)
Acetylcholine/metabolism , Aging , Cerebral Cortex/drug effects , Cognition Disorders/drug therapy , Phosphatidylserines/pharmacology , Pyrrolidines/pharmacology , Animals , Avoidance Learning/drug effects , Cerebral Cortex/analysis , Cerebral Cortex/metabolism , Corpus Striatum/analysis , Hippocampus/analysis , Rats , Scopolamine/antagonists & inhibitors , Scopolamine/pharmacology , Secretory Rate/drug effectsABSTRACT
The acquisition of a passive avoidance conditioned response was disrupted in the rat by electroconvulsive shock (ECS) and scopolamine administration. D,L-pyroglutamic acid (D,L-PCA) 500 and 1000 mg/kg, administered as arginine salt 120 min before the retest, prevented both the ECS and scopolamine-induced amnesia. Arginine alone was ineffective. Scopolamine brought about a 52 and 39% decrease, respectively, in cortical and hippocampal acetylcholine (ACh) levels, measured by means of a gas-chromatographic method. D,L-PCA 500 and 1000 mg/kg also prevented the decrease in brain ACh level. When the two isomers were studied separately, D-PCA was more effective than L-PCA and antagonized scopolamine-induced amnesia at the doses of 250 and 500 mg/kg. In conclusion, D,L-PCA is active on cortical and hippocampal cholinergic mechanisms and, like other 2-oxopyrrolidone derivatives, shows cognition-enhancing properties.
Subject(s)
Acetylcholine/metabolism , Brain Chemistry/drug effects , Electroshock , Memory/drug effects , Pyrrolidinones/pharmacology , Pyrrolidonecarboxylic Acid/pharmacology , Scopolamine/antagonists & inhibitors , Animals , Avoidance Learning/drug effects , Choline/metabolism , Conditioning, Operant/drug effects , Male , Memory/physiology , Rats , Rats, Inbred Strains , Scopolamine/pharmacology , StereoisomerismABSTRACT
The breakdown of the carbohydrates by the colonic bacterial flora can cause intestinal symptoms, such as meteorism, abdominal pain and diarrhoea. The ability of human bacterial flora to break down the DEAE-dextran, a new lipid lowering resin, similar to cholestyramine, was investigated in man. Colonic bacterial flora did not appear to break down DEAE-dextran, as assessed by hydrogen respiratory excretion measured in healthy volunteers. Furthermore, the blood levels of vitamin A, E and D (as 25-OH and 1,25-OH derivatives) were measured in patients treated with the DEAE-dextran in order to study the interference of DEAE-dextran on the absorption of liposoluble vitamins. With the exception of slightly depressed vitamin A levels in 3 patients out of 16, the blood values of the vitamins A, E and D were within the normal ranges, indicating that DEAE-dextran does not interfere with liposoluble vitamin absorption by the gut.
Subject(s)
DEAE-Dextran/adverse effects , Dextrans/adverse effects , Adult , Bile Acids and Salts/metabolism , Calcitriol/blood , Colon/metabolism , Colon/microbiology , Dietary Fats/metabolism , Humans , Hydrogen/metabolism , Hydroxycholecalciferols/blood , Methane/metabolism , Middle Aged , Vitamin A/blood , Vitamin E/bloodABSTRACT
The effect of cognition-enhancing agents oxiracetam and aniracetam on scopolamine-induced amnesia and brain acetylcholine decrease was investigated in the rat. Acetylcholine levels were measured by means of a gas-chromatographic method. Scopolamine (0.63 mg/kg IP 60 min before training) prevented the acquisition of a passive avoidance conditioned response ("step through": retest 30 min after training) and brought about a 64, 56 and 42% decrease in acetylcholine level in the cortex, hippocampus and striatum respectively. Oxiracetam (50 and 100 mg/kg IP) administered 30 min before scopolamine reduced the scopolamine-induced amnesic effect and decrease in acetylcholine level in the cortex and hippocampus, but not in the striatum. Lower and higher doses of oxiracetam were ineffective. Aniracetam (100 mg/kg PO) also prevented scopolamine-induced amnesia but attenuated acetylcholine decrease in the hippocampus only. Aniracetam (300 mg PO) reduced acetylcholine decrease in the hippocampus but did not prevent scopolamine-amnesia. In conclusion, oxiracetam and aniracetam exert a stimulatory effect on specific central cholinergic pathways. However, a direct relationship between cognition-enhancing properties and cholinergic activation needs further confirmation.
Subject(s)
Acetylcholine/analysis , Avoidance Learning/drug effects , Brain/drug effects , Pyrrolidines/pharmacology , Pyrrolidinones/pharmacology , Scopolamine/pharmacology , Animals , Brain/metabolism , Brain/physiology , Brain Chemistry/drug effects , Male , Rats , Rats, Inbred Strains , Reaction Time/drug effectsABSTRACT
The breakdown of the carbohydrates by the colonic bacterial flora can cause intestinal symptoms, such as meteorism, abdominal pain and diarrhoea. The ability of digestive enzymes and colonic bacterial flora to break down the DEAE-dextran, a new lipid lowering resin, was investigated in rats. DEAE-dextran appeared to be unaffected by either enzyme activity in the small intestine or bacterial flora in the large intestine. This may be important when dealing with the pharmacological activity of DEAE-dextran and estimating its side effects. Small intestinal transit rate appeared to be accelerated by oral DEAE-dextran in rats.
Subject(s)
DEAE-Dextran/metabolism , Dextrans/metabolism , Administration, Oral , Animals , Creatinine/urine , DEAE-Dextran/administration & dosage , Feces/analysis , Fluoresceins/urine , Gastrointestinal Transit , Intestinal Absorption , Intestine, Large/metabolism , Male , RatsSubject(s)
DEAE-Dextran/pharmacology , Dextrans/pharmacology , Lipid Metabolism , Menopause , Female , Humans , HysterectomyABSTRACT
In the rat, 1 min following electroshock (ECS) a 46 and 39% decrease in acetylcholine levels was found in the hippocampus and cerebral cortex, respectively. The decrease in the hippocampus was still statistically significant 30 min after ECS. The ECS applied 1 min after training also disrupted the performance of a passive avoidance conditioned response ('step down') tested 30 min later. Oxiracetam (100 and 300 mg/kg i.p.) administered 90 min before training prevented, in a dose-dependent manner, the decrease of acetylcholine in the cerebral cortex and hippocampus. Oxiracetam prevented the ECS disruption of the acquisition of a passive avoidance response. At the dose of 300 mg/kg the acetylcholine level 1 min after ECS was significantly higher than in the sham-treated rats. Piracetam at the same doses was inactive. These results support the hypothesis that oxiracetam may prevent the disruption of the conditioned response by acting on cortical and hippocampal cholinergic mechanisms.