Melatonin does not produce sedation in rats: A chronobiological study

ABSTRACT

Background: Melatonin has been associated with a wide variety of cellular, neuroendocrine, and neurophysiological processes. Clinical studies have reported the use of melatonin as an agent that exerts sedative-hypnotic effects. However, evidence of the sedative-hypnotic effects of different doses of melatonin is inconsistent, and available data regarding its night/day-time sedative effects are limited. The purpose of this study was to evaluate the effects of melatonin administered at different times of day on the magnitude of the sedative-hypnotic activity of different melatonin doses (5, 10, 30, and 50 mg/kg) in rats.

Methods: Sedation was assessed in Wistar rats behaviorally, using rota-rod, spontaneous locomotor activity, and fixed-bar tests at different times of day (ZT4, ZT10, ZT16, and ZT22).

Results: Our results showed that, compared to trazodone, acute and chronic dosing of ≤5 mg melatonin produced mild, transient sedative effects, mainly in the light period. Nevertheless, doses of ≥10 mg/kg did not cause sustained sedative effects.

Conclusion: These results suggest that melatonin may be used for sedation induction, mainly in preoperative patients.     

The urinary excretion of orally administered pteroyl-l-glutamic acid by the rat

1. The urinary excretion of folates after oral administration of [2-(14)C]pteroyl-l-glutamic acid was studied by assaying the radioactivity in the urine and in materials purified and characterized by t.l.c. 2. Radioactivity excreted was 6.8, 5.9 and 30.7% of the oral dose in the first 24h after doses of 3.1, 32 and 320mug/kg respectively. 3. Extensive decomposition of urinary folates to pteroyl-l-glutamic acid was prevented by antioxidants or collection of urine frozen. 4. At the three dosages, two major and one minor radioactive compounds were isolated. One of the major metabolites was 5-methyltetrahydropteroylglutamic acid. The others were unidentified but were not pteroylglutamic acid, 7,8-dihydro-, 5,6,7,8-tetrahydro-, 5- or 10-formyl-tetrahydro-, 5,10-methylidyne-tetrahydro-, 5-formimidoyl-tetrahydro-, 5,10-methylene-tetrahydro-, 5-methyltetrahydro-pteroylglutamic acid, nor any decomposition products of these compounds formed during isolation. Labelled unconjugated pteridines were absent. 5. Labelled pteroyl-l-glutamic acid was displaced by oral administration of unlabelled pteroyl-l-glutamic acid (1.6mg/kg) when given 3.5h after, but not when given 24h after the labelled dose. 6. The results show that orally administered [2-(14)C]pteroyl-l-glutamic acid is absorbed without metabolism and is then metabolized into naturally occurring tetrahydro-folates. 7. These findings are discussed with reference to previous work.     

Occupational exposure to anaesthetic gases and urinary excretion of D-glucaric acid

In order to ascertain whether the urinary excretion of D-glucaric acid (DGA) might be a suitable biomarker of effect in monitoring workers exposed to anaesthetic gases, we measured DGA before and after an operating session (and, in some workers, before and after a 2-week vacation) in 229 workers of surgical units and in 229 controls. In the former, we also measured urinary levels of nitrous oxide (N₂O) and isofiurane after at least 4 h of exposure. For all subjects, information on age, smoking habits, daily intake of alcohol, coffee, and drugs, history of liver or kidney disease was collected. Study subjects were ranked according to: exposure (class 0: subjects not exposed; class 1: N₂