From: Ian Goddard (Ian@Goddard.net)
Date: Sun Aug 15 1999 - 00:48:02 MDT
The first study below finds that very-high doses
of melatonin produced dose-dependent short-term
memory deficits possibly via the same mechanism
that Valium-class drugs (benzodiazepines) impair
memory. The doses were equal to .6 to 6.8 grams
for a 150-lb subject, very high! Interestingly,
and fortunately for melatonin consumers, the
second and third studies below found that
endogenous melatonin and exogenous doses of
melatonin in the standard-dose-range actually
facilitated memory. The forth study supports the
hypothesis that melatonin may be beneficial in
the treatment of Alzheimer's disease in part
by reducing the accumulation of beta-amyloid.
====================================================
Methods Find Exp Clin Pharmacol 1998 May;20(4):311-9
Evidence of GABAergic modulation in melatonin-induced
short-term memory deficits and food consumption.
Shaji AV, Kulkarni SK
Pharmacology Division, Panjab University,
Chandigarh, India.
Many of the pharmacological effects of melatonin
have been found to be similar to those of
benzodiazepines. In the present study, we analyzed
the role of melatonin on short-term memory retrieval
on transfer latency in elevated plus maze and food
consumption behavior, and the effects were compared
with those of diazepam. Melatonin dose-dependently
(10-100 mg/kg) produced short-term memory deficit
and it potentiated diazepam- (1 mg/kg) induced
cognitive deficit in mice. Flumazenil (1 and 4 mg/kg)
could reverse enhancement in diazepam-induced memory
deficit by melatonin. Chronic treatment with melatonin
(10 mg/kg/7d) produced a similar profile in transfer
latency on elevated plus maze compared with that of
diazepam. In a food consumption behavior study,
melatonin (25 and 50 mg/kg) produced a significant
hyperphagic effect compared to control. Flumazenil
(4 mg/kg) could significantly reverse the hyperphagic
effects induced by diazepam (2 mg/kg), but would
be insignificant with regard to that due to melatonin.
These findings provide further evidence that some of
the pharmacological effects of melatonin are
comparable with those of diazepam and may involve
central GABAergic mechanism.
================================================
European Journal of Pharmacology
1998 May 22;349(2-3):159-62
Melatonin facilitates short-term memory.
Argyriou A, Prast H, Philippu A
Department of Pharmacology and Toxicology,
University of Innsbruck, Austria.
The olfactory social memory test, based on the
recognition of a juvenile rat by a male adult
rat, was used to investigate whether melatonin
influences memory. Intracerebroventricular
(i.c.v.) injection of 1.1 nmol melatonin
shortened recognition time, while the melatonin
ML1 receptor antagonist luzindole (1 nmol)
exerted the opposite effect. The facilitating
influence of melatonin was abolished in the
presence of 0.5 nmol luzindole. The findings
suggest that endogenous melatonin facilitates
short-term memory.
==================================================
Journal of Pineal Research 1998 Oct;25(3):177-83
Melatonin effects on sleep, mood, and cognition
in elderly with mild cognitive impairment.
Jean-Louis G, von Gizycki H, Zizi F
Department of Psychiatry, University of California,
San Diego, USA. gjeanlouis@ucsd.edu
The effects of immediate-release melatonin on
circadian rest-activity profiles, cognition, and
mood were investigated in ten elderly individuals
with self-reported sleep-wake disturbances.
Melatonin (6 mg), administered 2 hr before habitual
bedtime, enhanced the rest-activity rhythm and
improved sleep quality as observed in a reduction
in sleep onset latency and in the number of
transitions from sleep to wakefulness. However,
total sleep time was not significantly increased
nor was wake within sleep significantly reduced.
The ability to remember previously learned items
improved along with a significant reduction in
depressed moods. No side effects or contraindications
were reported by any of our participants during the
10 day trials. These data suggest that melatonin can
safely improve some aspects of sleep, memory, and
mood in the elderly in short-term use.
====================================================
TITLE: Monozygotic twins with Alzheimer's disease
treated with melatonin: Case report.
AUTHORS: Brusco LI; Marquez M; Cardinali DP
AUTHOR AFFILIATION: Departamento de Fisiologia, Facultad
de Medicina, Universidad de Buenos Aires, Argentina.
SOURCE: J Pineal Res 1998 Dec;25(4):260-3
CITATION IDS: PMID: 9885996 UI: 99101087
ABSTRACT: Monozygotic twins with Alzheimer's disease
of 8 years duration were studied. The onset of the
disease differed by about 6 months between twins and
was characterized by a primary impairment of memory
function. Clinical evaluation at the time of diagnosis
indicated a similar cognitive and neuroimaging alteration
in both patients, as well as a similar neuropsychologic
impairment. A possible genetic origin of the disease was
suggested by a similar disease suffered by the mother.
Patients were initially treated with vitamin E
(800 I.U./day). Starting at approximately the same time
(about 3 years ago), they received 50 mg/day thioridazine
because of the behavioral and sleep disorder. One of the
patients was treated with melatonin (6 mg orally) at bed
time daily for 36 months. Evolution of the disease in the
melatonin-treated patient indicated a milder impairment
of memory function, with substantial improvement of
sleep quality and reduction of sundowning. This led to
discontinuance (after 3 months) of thioridazine treatment.
Present clinical evaluation indicated a difference in
functional stage of the disease between the twins
(Functional Assessment Tool For Alzheimer's Disease,
FAST), with a score of 5 in the twin who received
melatonin and of 7b in the twin who did not receive it.
Since experimental data on melatonin in animals indicated
its antioxidant, antiapoptotic, and beta-amyloid-decreasing
activity, the hypothesis that melatonin has a beneficial
effect in Alzheimer's disease patients should be considered.
Acessed via PubMed http://ncbi.nlm.nih.gov/PubMed
and MedLine http://igm.nlm.nih.gov
------------------------------------------------------------
GODDARD'S JOURNAL: http://www.erols.com/igoddard/journal.htm
____________________________________________________________
This archive was generated by hypermail 2.1.5 : Fri Nov 01 2002 - 15:04:46 MST