ABSTRACT
The pharmacokinetics of rokitamycin tablets were studied in 12 healthy volunteers in a randomized cross-over design. The doses tested were 200 mg, 300 mg, 400 mg and 600 mg, as single oral administration. Rokitamycin was absorbed quickly with Tmax for all doses around 30 min after drug intake. Total AUC and Cmax values were linearly related to the administered dose. The buffer formulation determined a low interindividual variation. The overall findings show a good similarity with the data obtained in Japanese subjects. Tolerability was very good.
Subject(s)
Miocamycin/analogs & derivatives , Administration, Oral , Adult , Drug Administration Schedule , Female , Humans , Male , Miocamycin/administration & dosage , Miocamycin/pharmacokinetics , Reference ValuesABSTRACT
The substituted 3-aminoxyproprionyl (VII) and 3-aminoxy-(E)-2-methoxyiminopropionyl monobactams (VIII) which possess the monocyclic beta-lactam nucleus of aztreonam (IX) were synthesized by reaction of triethylammonium (3S, 4S)-3-amino-4-methyl-2-oxo-1-azetidinsulfonate with the aminoxy acids X and XI, respectively. Compounds VII and VIII were assayed in vitro for their antimicrobial properties against Gram-positive and Gram-negative bacteria, whether producers of beta-lactamases or otherwise. Both types of compounds (VII and VIII) exhibited a poor antibacterial activity towards Gram-positive bacteria, comparable to that of aztreonam. On the contrary VII and VIII proved to be practically inactive against Gram-negative microorganisms, towards which aztreonam exhibits a high degree of activity.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Monobactams/chemical synthesis , Aztreonam/pharmacology , Chemical Phenomena , Chemistry , Freeze Drying , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Microbial Sensitivity Tests , Monobactams/pharmacology , Spectrophotometry, InfraredABSTRACT
A number of N-substituted 4-hydroxy-, 4-acyloxy- and 4-alkoxy-2-pyrrolidinones were examined by a screening method predictive of their activity on cognitive processes. The 1-aminocarbonylmethyl-substituted compounds showed a favorable effect on learning and memory, and among them the most active was the 4-hydroxy derivative, oxiracetam, which had a potency considerably higher than piracetam, used for comparison purposes.
Subject(s)
Learning/drug effects , Memory/drug effects , gamma-Aminobutyric Acid/analogs & derivatives , Amnesia/prevention & control , Animals , Chemical Phenomena , Chemistry , Electroshock , Humans , Lethal Dose 50 , Male , Mice , Rats , Rats, Inbred Strains , gamma-Aminobutyric Acid/chemical synthesis , gamma-Aminobutyric Acid/pharmacologyABSTRACT
Rats were rendered epileptic by subpial injection of an FeCl3 solution. Epileptiform discharges, recorded by chronically implanted extradural electrodes, were evident within 48 h of surgery and persisted for more than 6 months. It is demonstrated that this model is useful for studying new antiepileptic agents since a series of clinically effective drugs (diazepam, clonazepam, Na phenobarbital, primidone, carbamezepine, ethosuximide, diphenylhydantoin, Na valproate, GABOB) show an activity which is does-dependent and within a range satisfactorily related to human dosages.
Subject(s)
Anticonvulsants/pharmacology , Seizures/drug therapy , Animals , Chlorides , Chronic Disease , Clonazepam/pharmacology , Diazepam/pharmacology , Disease Models, Animal , Drug Evaluation, Preclinical , Electroencephalography , Ferric Compounds/pharmacology , Male , Rats , Rats, Inbred Strains , Seizures/chemically inducedABSTRACT
A series of substances from different pharmacological classes was examined by two different tests for their activity on learning and memory. A concomitant evaluation was performed by use of a one-trial passive avoidance immediately followed by electroshock in mice and the pole-climbing test in rats. Only doses not producing changes in gross behavior (Irwin's test) were used. A facilitating action on all the considered parameters was observed for d-amphetamine, caffeine, L-glutamine, Mg pemoline, phosphorylserine, piracetam, strychnine, and tricyanoaminopropene. A worsening action was found for atropine, cycloheximide, diazepam, and morphine. Chlorpheniramine, diphenylhydantoin, GABA, imipramine, meclizine, mescaline, metrazol, and testosterone showed no or doubtful activity. Our results suggest that the parallel use of these relatively simple tests supplies information that is satisfactory for screening purposes and that has a high degree of predictability as substantiated by literature data.
