ABSTRACT
We conducted an open-label pilot study of dextromethorphan (DM) in intractable partial epilepsy with the following objectives: a preliminary evaluation of the drug's safety and efficacy in the epileptic patient and a definition of a concentration range which can be safely achieved in future studies. Sixteen patients with drug-resistant, localization-related epilepsies entered the trial. After an 8-week baseline period, DM was added to the existing antiepileptic drugs at a dose of 40 and 50 mg every 6 h (160 and 200 mg/day). Each treatment period lasted 8 weeks. Seizure control improved after administration of DM, especially in the group of intermediate and slow metabolizers. Two patients, however, experienced increased seizure frequency and withdrew from the study. Adverse effects during DM administration were mild and transient. DM was well tolerated even in patients with high plasma levels of the drug (up to 15020 ng/dl). Our results indicate that DM is safe and effective in the treatment of comedicated patients with intractable partial epilepsies.
Subject(s)
Anticonvulsants/therapeutic use , Dextromethorphan/therapeutic use , Epilepsies, Partial/drug therapy , Adult , Anticonvulsants/adverse effects , Anticonvulsants/pharmacokinetics , Dextromethorphan/adverse effects , Dextromethorphan/pharmacokinetics , Drug Resistance , Female , Humans , Male , Phenotype , Pilot ProjectsABSTRACT
Aminoglycoside antibiotics inhibit contractility of the isolated guinea pig vas deferens in a dose-related manner. However, total inhibition of the contractility cannot be attained, a phenomenon most probably attributed to the partial inhibition of the function of Ca channels by the antibiotics. The inhibitory potency of aminoglycoside antibiotics was found to be: sisomicin greater than gentamicin greater than netilmicin greater than streptomycin greater than dactimicin greater than amikacin greater than kanamycin greater than kanendomycin greater than dibekacin greater than tobramycin. Ca2+ antagonize the action of aminoglycoside antibiotics on the vas deferens competitively. This observation indicates that the untoward effect of aminoglycoside antibiotics on contractility of the vas deferens can be attributed to their ability to interfere with Ca2+ entry through cell membranes of the tissue, a prerequisite for subsequent contraction. Above a specific threshold (7.5 mM) Ca2+ have a prophylactic effect on vas deferens and prevent the inhibitory action of ICmax doses of the antibiotics. Thus, Ca could be used as a prophylactic medium or as an antidote in restoring contractility of the vas deferens if it is inhibited by aminoglycoside antibiotics.
Subject(s)
Anti-Bacterial Agents/pharmacology , Muscle, Smooth/drug effects , Animals , Calcium/metabolism , Gentamicins/pharmacology , Guinea Pigs , In Vitro Techniques , Male , Muscle Contraction/drug effects , Vas Deferens/drug effectsABSTRACT
Kinetic analysis of cGMP phosphodiesterase activity in the rat brain indicated that Km values did not differ significantly with sex, age (1 to 270 days old), or brain area (amygdala, cerebellum, cerebral cortex, hypothalamus, thalamus, reticular formation). There was no dimorphism in enzyme activity between normal or artificially mimicked gender, nor was there any significant variation in activity following short or long term alterations of endogenous levels of gonadal hormones in any of the brain regions investigated. Highest activity was observed in cerebral cortex and amygdala. Maturation caused a significant increase in enzyme activity, the adult levels being reached by the 38th to 40th day of life.
Subject(s)
3',5'-Cyclic-GMP Phosphodiesterases/analysis , Brain/enzymology , Gonadal Steroid Hormones/physiology , Adenylyl Cyclases/analysis , Age Factors , Animals , Castration , Estrus , Female , Gonadal Steroid Hormones/pharmacology , Kinetics , Male , Pregnancy , Rats , Rats, Inbred StrainsABSTRACT
High affinity binding of [3H]-dopamine was measured in membrane fractions prepared from cerebral cortex, amygdala, hypothalamus, thalamus and reticular formation of female rats aged 1 to 260 days old. [3H]-dopamine bound with approximately 30 x 10(-9) M affinity to neural membrane fractions of female brains of any age. [3H]-dopamine binding increased with age either in a sigmoid fashion, as was the case in the amygdala, hypothalamus and reticular formation, or in a parabolic fashion, as was the case in the cerebral cortex and thalamus, the adult levels being reached on the 30th and 70th day of life respectively.
