Analysis of the actions of alprenolol and propranolol on the beta adrenergic receptors controlling heart rate in the anaesthetized cat.
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Acute changes in spontaneous motor activity, the EEG and photically induced epileptic responses have been observed in baboons (Papio papio) following the i.v. injection of drugs acting on dopaminergic transmission. Apomorphine hydrochloride, 0.5-1.0 mg/kg, produced a phase of acute excitement with accentuated vigilance and abnormal buccal motor activity lasting 30-40 min; during this phase myoclonic responses to intermittent photic stimulation were absent. After piribedil (ET 495, 1,2'' -pyrimidyl-4-piperonylpiperazine), 2-10 mg/kg, acute excitement was not seen. Intermittent delta activity was prominent in the EEG for 1-3 hr, and was associated with a slight reduction in photically induced epileptic responses. Haloperidol 0.6-1.2 mg/kg, produced a long-lasting reduction in spontaneous motor activity with an increased incidence of spontaneous EEG spikes and waves and a great enhancement of paroxysmal EEG activity during photic stimulation. Pimozide, 0.5-2.5 mg/kg, normally produced mild sedation and some EEG slowing. 2 animals responded idiosyncratically to both haloperidol and pimozide, displaying intermittent dystonic episodes with bucco-facial dyskinesia. These findings suggest that activation of dopaminergic receptors can lead to a reduction in myoclonic responses to photic stimulation.
Clinical studies suggest that deprenyl may retard the progression of Parkinson's disease, an effect that may be related to its monoamine oxidase (MAO) inhibiting properties. Deprenyl also protects against the neurodegenerative effects of the noradrenergic toxin DSP-4. In this study we investigated the role of MAO B inhibition in this protection. C57BL/6 mice were given DSP-4 (50 mg/kg i.p.) 1 h. 24 h or 4 days after the administration of deprenyl (10 mg/kg i.p.) or the selective MAO B inhibitor MDL 72974 (1.25 mg/kg), and then killed 1 week later for assay of hippocampal norepinephrine. The MAO B inhibiting effects of deprenyl or MDL 72974 were also determined after these same intervals of time. Deprenyl and MDL 72974 produced comparable degrees of enzyme inhibition 1 h (greater than 95%), 24 h (greater than 90%) or 4 days (greater than 70%) after their administration. Given 1 h before, deprenyl totally blocked the norepinephrine-depleting effects of DSP-4, but this protection declined sharply when 24 h or 4 days was allowed to elapse between deprenyl and DSP-4 administration. MDL 72974 failed to protect at any time point. In vitro, we detected no activity using DSP-4 as a substrate for MAO. These findings suggest that the ability of deprenyl to protect against DSP-4-induced neuronal degeneration may not depend on its MAO B inhibiting properties.
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SUMMARY: The effect of garlic and onion on alimentary hyperlipemia, induced by feeding 100 g butter, has been studied in 10 healthy subjects. The freshly extracted juice of 50 g of garlic or onion, as well as an equivalent amount of their ether-extracted essential oils, was administered randomly on four different days during a one-week period. Garlic and onion have a significant protective action against fat-induced increases in serum cholesterol and plasma fibrinogen and decreases in coagulation time and fibrinolytic activity. The essential oil fraction, which contains all the taste and odour, exactly duplicated the beneficial effects of whole garlic and onion. It is, therefore, concluded that the active principle of garlic and onion is the essential oil, which chemically is a combination of sulphur-containing compounds, mainly allyl propyl disulphide and diallyl disulphide.
Methylamine can be converted by semicarbazide-sensitive amine oxidase (SSAO) to formaldehyde and hydrogen peroxide, which have been proven to be toxic towards cultured endothelial cells. We investigated whether or not these deaminated products from methylamine can exert potentially hazardous toxic effects in vivo. Long lasting residual radioactivity in different tissues was detected following administration of [14C]-methylamine in the mouse. Approximately 10% of the total administered radioactivity could even be detected 5 days after injection of [14C]-methylamine. Eighty percent of the formation of irreversible adducts can be blocked by a highly selective SSAO inhibitor, (E)-2-(4-fluorophenethyl)-3-fluoroallylamine hydrochloride (MDL-72974A). The residual radioactivity was primarily associated with the insoluble tissue components and the soluble macromolecules. Radioactively labelled macromolecules were fragmented following enzymatic proteolysis. Results suggest that the formaldehyde derived from methylamine interacts with proteins in vivo. In the streptozotocin-induced diabetic mice, both SSAO activity and the formation of residual radioactivity were found to be significantly increased in the kidney. Chronic administration of methylamine enhances blood prorenin level, which strongly suggests that uncontrolled deamination of methylamine may be a risk factor for initiation of endothelial injury, and subsequent genesis of atherosclerosis.
The use of single-column ion chromatography with conductometric detection was shown to be useful for the analysis of sulfonium and selenonium ions. A Hamilton PRP X-200 cation column was eluted with either solvent A (5 mM nitric acid in 30% methanol) or solvent B (4 mM nitric acid). With solvent B, trimethylsulfonium ion was separated from trimethylselenonium ion. With solvent A, amounts of trimethylsulfonium ion from 2 to 250 nmol were detected with a linear response. The retention times and response factors for a series of sulfonium ions with various organic groups were determined. In general the ions with more hydrophobic groups eluted later, but all had similar response factors. The method was shown to be useful for optimizing conditions for the synthesis of methylsulfonium ions, specifically the reaction of methyl iodide with diallyl sulfide.
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