O-methyltransferase Inhibitors Research Articles

Potentiation of the l-Dopa effect in man by the use of catechol- O-methyltransferase inhibitors

A potent COMT inhibitor ( N-butyl gallate, GPA 1714) has been found effective in counteracting the toxic dose-related side-effects of l-Dopa therapy in patients with Parkinsonism. This drug was found effective also in relieving involuntary movements in a small group of patients with Huntington's chorea and spasmodic torticollis. The biochemical mechanism and implications of these diseases are as yet unknown. A possible relationship to disturbed monoamine metabolism is suggested by this clinical study.

Perfusion of rat's liver with blood: transmitter overflows and gluconeogenesis.

A simplified apparatus for the perfusion of the isolated rat liver is described. The operative technique has been developed so as to avoid any interruption in the blood supply to the liver. By the generally accepted criteria of viability the liver remains almost normal for up to 4 h. Perfusion with oxygenated blood through both the hepatic artery and portal vein confers no special advantages over portal perfusion alone, as judged by lactate utilization. No overflows of sympathetic transmitter could be detected from the perfused liver of the rat after nerve stimulation unless catechol- O -methyl transferase inhibitors were present; even in the presence of phenoxybenzamine (to block transmitter uptake by nerve endings) overflows were small. Larger transmitter overflows were obtained from the perfused liver of guinea-pig. Nerve stimulation caused a transient increase in the rate of gluconeogenesis by the rat liver; the maximum response, an increase of 60 %, occurred after 5 min stimulation at a frequency of 10 Hz.

The effect of dopa, α-methyldopa and reserpine on the dopamine content of the brain of the snail, Helix aspersa

1. 1. Paper chromatographic analysis using five different solvent systems and spectrophotofluorimetry reveal the presence of 5·5 μg/g dopamine in teh circumoesophageal ganglionic mass of Helix aspersa, and 0·18 μg/ml DOPA in the blood. 2. 2. Injection of reserpine decreased the brain dopamine content. 3. 3. Injection of DOPA increased the brain dopamine content. 4. 4. Amine oxidase inhibitors and o-methyl transferase inhibitors have no effect on brain dopamine content. 5. 5. Dopamine was the only catecholamine found in the nervous system of the crab Carcinus maenas and the clam mercenaria mercenaria. No catecholamine was found in the ventral nerve cord of the leech Hirudo medicinalis.

Monoamine oxidase and catechol O-methyl transferase inhibitors. Effect of intradermal injection on exogenous and endogenous norepinephrine.

Introduction In a previous paper we reported on the physiologic effect of a variety of norepinephrine derivatives (catecholamines) introduced into normal and diseased skin. 2 Small differences in the chemical structure of these closely related compounds resulted in vastly different physiologic reactions. This communication concerns an effort to study some of the biologic mechanisms in human skin which participate in the metabolic inactivation of exogenous norepinephrine (see Fig. 1). Attempts to elicit evidence for the presence of endogenous catechol sympathomimetic amines will also be reported. In a search of the literature we were unable to find direct evidence which would definitely support the idea that norepinephrine is present in human skin. It is generally assumed that this physiologic metabolite is present in human skin. 3 Recent workers, using histochemical and electron microscope techniques, have found indirect evidence of the presence of epinephrine-like substances, 4,5 but there is still no