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Membrane association of N-oleoyl-dopamine in rat brain

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N-oleoyl-dopamine (OLDA) belongs to a novel class of bioactive amides of fatty acids. The compound, a lipid derivative of dopamine, holds promise as a potential prodrug or carrier of dopamine into the brain. In this context, a key issue concerning OLDA is the integrity of the compound once it enters the brain. We addressed this issue in the current study by assessing the propensity of OLDA for hydrolysis in rat brain tissue in vitro. The brains were dissected from surgically anesthetized rats after they had been sacrificed by perfusion with physiological saline through the heart. Membrane fractions of brain tissue were isolated and incubated with 1 mmol/l OLDA. Stability of the OLDA molecule was assessed from the spectrophotometric recordings of OLDA spectra in membrane fractions at hourly time points for up to 24 hours. The methodological assumption was that any major change in the shape of the OLDA spectrum would point to a structural, and thus also possibly functional, alteration of the molecule. We found that the OLDA spectrum remained unchanged in the assays for up to 17 h of incubation. We conclude that OLDA strongly resists hydrolysis in brain membrane fractions. The results suggest that dopamine-like biological effects of OLDA might have to do with the interaction of the integral OLDA compound, rather than a dissociated-off dopamine moiety, with the dopaminergic system.
This review summarizes some of the recent findings concerning the long-held tenet that the enzyme, N-acetyltransferase, which is involved in the production of N-acetylserotonin, the immediate precursor of melatonin, may in fact not always control the quantity of melatonin generated. New evidence from several different laboratories indicates that hydroxyindole-O-methyltransferase, which O-methylates N-acetylserotonin to melatonin may be rate-limiting in some cases. Also, the review makes the point that melatonin's actions are uncommonly widespread in organs due to the fact that it works via membrane receptors, nuclear receptors/binding sites and receptor-independent mechanisms, i.e., the direct scavenging of free radicals. Finally, the review briefly summarizes the actions of melatonin and its metabolites in the detoxification of oxygen and nitrogen-based free radicals and related non-radical products. Via these multiple processes, melatonin is capable of influencing the metabolism of every cell in the organism.
Vindoline and its analogues are important constituents of the Madagascan periwinkle Catharanthus roseus, and some of them are valuable chemotherapy drugs used in treatment for some types of cancer, including leukaemia, lymphoma, breast and lung cancer. The search for semi-synthetic congeners of natural substances is still an important task for organic chemistry. In this communication we report the synthesis of five new vindoline derivatives, 15-(2-methoxyphenyl)vindoline 11, 15-(3-methoxyphenyl)vindoline 12, 15-(2-nitrophenyl)vindoline 13, 15-(3-cyanophenyl)vindoline 15, and 15-(4-cyanophenyl)vindoline 16 using the Suzuki-Miyaura reaction as the key step. X-Ray analysis of compound 16 is also reported
This brief resume enumerates the multiple actions of melatonin as an antioxidant. This indoleamine is produced in the vertebrate pineal gland, the retina and possibly some other organs. Additionally, however, it is found in invertebrates, bacteria, uni­cellular organisms as well as in plants, all of which do not have a pineal gland. Melatonin's functions as an antioxidant include: a), direct free radical scavenging, b), stimulation of antioxidative enzymes, c), increasing the efficiency of mitochondrial oxidative phosphorylation and reducing electron leakage (thereby lowering free radical generation), and 3), augmenting the efficiency of other antioxidants. There may be other functions of melatonin, yet undiscovered, which enhance its abil­ity to protect against molecular damage by oxygen and nitrogen-based toxic reac- tants. Numerous in vitro and in vivo studies have documented the ability of both physiological and pharmacological concentrations to melatonin to protect against free radical destruction. Furthermore, clinical tests utilizing melatonin have proven highly successful; because of the positive outcomes of these studies, melatonin's use in disease states and processes where free radical damage is involved should be in­creased.
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