Evidence for a selective inhibition by FLA 336(+) of the monoamine oxidase in serotonergic neurones in the rat brain.
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Animals↗
Biomedical subjects
A L Ask
Publications and source records attributed to A L Ask.
Structural requirements for uptake into serotoninergic neurones.
Experiments were performed to examine whether non-hydroxylated tryptamines and 4-chloroamphetamine utilize the membrane 5-hydroxytryptamine carrier to pass into serotoninergic neurones. The accumulation and deamination of 14C-tryptamine by mouse brain slices or homogenates of rat hypothalamus were not inhibited by cocaine or norzimelidine, a selective inhibitor of the neuronal 5-HT uptake. The prevention by alpha-methyltryptamine (10 mg/kg, intraperitoneally), alpha-ethyltryptamine (20 mg/kg intraperitoneally) and 4-chloroamphetamine (20 mg/kg intraperitoneally) of the irreversible inhibtion of monoamine oxidase by pheniprazine (2.5 mg/kg intraperitoneally) and clorgyline (5 mg/kg intraperitoneally) in serotoninergic synaptosomes from mouse brain was not antagonized by pretreatment of the animals with norzimelidine (20 mg/kg intraperitoneally). The partial preventing effect of alpha-ethyl-4-methyl-m-tyramine (H 75/12)(2 X 50 mg/kg intraperitoneally) was, on the other hand, antagonized by norzimelidine. These results do not support the hypothesis that non-hydroxylated tryptamines and 4-chloroamphetamine are transported by the 5-HT carrier.
Animals↗
Platelet monoamine oxidase in a pedigree with schizophrenia: an interlaboratory project.
Conflicting reports on the association between platelet MAO activity and schizophrenia prompted a critical review and determinations on identical samples at one laboratory in Sweden and one in the U.S.A. Samples originated from eight schizophrenics and 27 relatives belonging to a large pedigree, thus ensuring biological homogeneity. In the USA laboratory, a significantly lower MAO activity was found in the schizophrenics when benzylamine or beta-phenylethylamine was used as substrate (but not with tryptamine), while a similar result was obtained in the Swedish laboratory when tryptamine was used (but not with benzylamine or beta-phenylethylamine). Comparisons between materials examined in different laboratories do not seem meaningful until differences in methodologies have been clarified. At present there is neither proof nor disproof of MAO being a "genetic marker" for vulnerability to the schizophrenic disorder.
Benzyl Compounds↗
Selective monoamine oxidase inhibitors. 1. Compounds related to 4-aminophenethylamine.
A series of derivatives of 4-aminophenethylamine was synthesized and their effect on monoamine oxidase (MAO) activity in the brain was evaluated. Several of the new compounds were potent and selective inhibitors of the A form of MAO but were poor inhibitors of the B form. The most active compounds were the 2,6-dichloro-(9) and the 2-halogeno-4-dimethylaminophenethylamines (5, 6, and 8). Some of the compounds also strongly antagonized aggressive behavior in isolated male mice. This effect was correlated to the MAO inhibition when tyramine was used as substrate. Significant correlations between MAO inhibition in vivo and potentiation of the syndromes produced by 5-hydroxytryptophan and tryptamine and antagonism of reserpine sedation were obtained.
5-Hydroxytryptophan↗
Comparative local anesthetic efficacy and pharmacokinetics of epidurally administered ropivacaine and bupivacaine in the sheep.
BACKGROUND AND OBJECTIVES: Ropivacaine is the S(-) propyl homolog of bupivacaine and mepivacaine. Studies in humans have confirmed the results of studies in laboratory animals that ropivacaine is a long-acting local anesthetic with an anesthetic profile similar to bupivacaine. Acute, intravenous systemic toxicity studies have been conducted in sheep and dogs. Local anesthetic efficacy has been studied after epidural administration in the dog. This study was initiated to determine the local anesthetic efficacy and pharmacokinetics of ropivacaine and bupivacaine after epidural administration in an experimental sheep model and to evaluate the sheep model as a model of experimental epidural anesthesia. METHODS: Twelve adult nonpregnant ewes were prepared with chronically implanted lumbar epidural catheters and arterial lines. Each sheep received injections of 5.0 mL ropivacaine and bupivacaine (0.5% and 0.75%) in a blinded, random, cross-over fashion. Onset and duration of sensory and motor blockade were evaluated. Arterial blood samples were drawn for serum drug concentration determinations and pharmacokinetic analysis. RESULTS: Onset and duration of motor blockade were similar for comparable concentrations of both drugs. Both concentrations of ropivacaine and bupivacaine 0.5% demonstrated differential neural blockade. The peak serum concentrations generally occurred within 8 minutes after administration. The terminal elimination half-life in serum was about 3.5-4.0 hours and 6 hours for ropivacaine and bupivacaine, respectively. No signs of systemic toxicity were observed. Results of sensory and motor blockade were consistent with previous studies in laboratory animals and humans. CONCLUSIONS: Ropivacaine produces sensory and motor blockade which is similar to that produced by equal concentrations of bupivacaine after epidural administration in the sheep. Peak serum concentrations produced no signs of systemic toxicity. The results of this study are consistent with previously published data from studies in laboratory animals and humans. The sheep model of experimental epidural anesthesia appears to be a clinically relevant method to evaluate experimental local anesthetics.
Amides↗