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Biomedical subjects

A A Manian

Publications and source records attributed to A A Manian.

At least 37 records · Page 2Linked to original sources
PubMed1976

Metal chelates of L-DOPA for improved replenishment of dopaminergic pools.

An exploratory study consisting of physiochemical and animal experiments was undertaken with the objective of developing one or more metal-L-DOPA chelate systems for an improved transport of L-DOPA into the brain. This approach is based on a theoretical speculation that the pyridoxal-dependent decarboxylation of L-DOPA in the precerebral areas might be obviated by an appropriate metal chelation of the aminocarboxylate end of the L-DOPA molecule. Equilibium studies on the interactions of L-DOPE with Cu2+,Zn2+, Co2+, Mg2+ and Fe2+ ions and their ATP chelates were carried out in order to examine the conditions for the selective binding of the terminal amine group. Metal chelate systems for in vivo transport experiments were selected viz., Cu2+ or Zn2+-L-DOPA (1:2) and Cu2+ or Zn2+-ATP-L-DOPA (1:1:1) which contained the amine-bound metal ion in a completely coordinated form. Results of in vivo studies involving the intraperitoneal administration of 14C-and 3H-LABELED L-DOPA compounds have shown a 100-150% increase in the transport of L-DOPA into the brain by using the Cu2+ and Zn2+ chelates over that effected by using the unchelated L-DOPA. A chromatographic analysis of the brain homogenates showed that only 6% of the overall radioactivity of the brain could be attributed to 3-methoxytyrosine, and the remaining activity was due to DOPA, dopamine and norepinephrine. The transport effectiveness was also compared with that obtained by using the combination drug, RO4-4602 + L-DOPA.

Animals↗
PubMed1976

Effects of neuroleptic agents on cyclic GMP in rat cerebral cortex.

Cyclic guanosine 3' ,5'-monophosphate(cyclic GMP) levels were increased in incubated tissue slices from rat cerebral cortex in response to added cholinomimetic agents (carbachol and choline chloride) and neuroleptic compounds (chlorpromazine, 8-hydroxychlorpromazine, 7-hydroxychlorpromazine methiodide, haloperidol, thioridazine, chlorpromazine sulfoxide and promethazine). Calcium ion was required for this effect. Moreover, selected agents namely, 7,8-dihydroxychlorpromazine, 7,8-dimethoxychlorpromazine, chlorpromazine and clozapine prevented the rise in cyclic GMP induced by carbachol.

Animals↗
PubMed1975

Effects of superoxide dismutase on the auto-oxidation of 7, 8-dihydroxychlorpromazine in the presence of rat brain mitochondria.

7,8-Dihydroxychlorpromazine 7,8-diOH-CPZ) is known to undergo auto-oxidation when exposed to air. Hydrogen peroxide is formed during this process, and the amount formed can be calculated from the amount of oxygen produced upon the addition of catalase. In the presence of superoxide dismutase the rate of oxidation of the CPZ metabolite is accelerated, accompanied by an increased production of hydrogen peroxide. When similar incubation are carried out with rat brain mitochondria present, hydrogen peroxide production is no longer detectable. The implications of this finding with regard to in vivo hydrogen peroxide production during the auto-oxidation of 7,8-diOH-CPZ are discussed. A preliminary report has been presented (1).

Animals↗