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Recent Patents on CNS Drug Discovery
ISSN: 1574-8898
Upcoming Articles
Contemporary Anticholinesterase Pharmaceuticals of
Natural Origin and Their Synthetic Analogues for the Treatment
of Alzheimer’s Disease
Gürdal Orhan, Ilkay Orhan, Nese Subutay-Öztekin,
Fikri Ak, Bilge Şener
[Abstract]
The Role of Melatonin in the Immuno-Neuro-Psychology
of Mental Disorders
Maria D. Maldonado, Maria A. Pérez-San-Gregorio
and Russel J. Reiter
[Abstract]
Multitasking of Neuropeptide Y through the Lens of
Motifs
Michael Myslobodsky
[Abstract]
Recent Advancements in Anti-Migraine Drug Research:
Focus on Attempts to Decrease Neuronal Hyperexcitability
Hedvig Bölcskei, Bence Farkas, Pál
Kocsis, István Tarnawa
[Abstract]
Humanin; A Defender Against Alzheimer’s Disease?
Masaaki Matsuoka
[Abstract]
Abstracts
[Back to top]
Contemporary Anticholinesterase Pharmaceuticals of Natural
Origin and Their Synthetic Analogues for the Treatment of
Alzheimer’s Disease
Gürdal Orhan, Ilkay Orhan, Nese Subutay-Öztekin,
Fikri Ak, Bilge Şener
Alzheimer’s disease (AD), the most common form
of dementia, is a degenerative and progressive neurological
disorder characterized by deficit in the cholinergic transmission
and formation of senile plaques containing β-amyloid
protein in the brain. Although complete pathology of the disease
has not been fully elucidated yet, there are several treatment
strategies for AD treatment. The complexity of AD is also
due to involvement of several enzymes through its progression.
Therefore, the most important therapeutic approach has emerged
as inhibition of acetylcholinesterase (AChE), which is the
key enzyme in the breakdown of acetylcholine. Another very
attractive approach to lower
β-amyloid protein in fibrillar form has been
the α-
and β-secretase
inhibitors. On the other hand, recently, N-methyl-D-aspartate
(NMDA) receptor antagonists have become a strong alternative,
which has been approved to be effective in treatment of moderate
to severe type of AD. Within the past few years, some pharmaceuticals
have become available for clinical use; however, none of them
have been shown to possess ability to discontinue the disease
up to date. Hence, there is obviously a great need for discovery
of new drug candidates of natural or synthetic origins for
AD treatment. This review will cover AChE-inhibiting pharmaceuticals
from plants and their synthetic derivatives including relevant
patent literatures which may promise a future hope for AD
treatment.
[Back to top]
The Role of Melatonin in the Immuno-Neuro-Psychology of Mental
Disorders
Maria D. Maldonado, Maria A. Pérez-San-Gregorio
and Russel J. Reiter
Melatonin (N-acetyl-5-methoxytryptamine) is
a molecule known to be produced in multiple cells and organs.
It acts at the level of the biological clock, the suprachiasmatic
nuclei, to modulate their activity, thereby influencing circadian
rhythms, and also sleep processes. The clinical application
of melatonin in the treatment of human mental disorders is
still in its infancy. Until now, melatonin only has been used
in psychiatry because of its hypnotic, resynchronizing and
antioxidant actions. In this review, we hypothesized that
melatonin might play an important role as an adjuvant therapy,
in mental disturbances, due to other properties including
its anti-inflammatory, antinociceptive, anxiolytic, drug detoxification
properties, protective actions against osteoporosis, etc.
Complex interactions occur between the brain and the immune
system and currently is accepted that psychological and psychiatric
illness can compromise immune and hormonal functions. Altered
psychological states often influence the susceptibility of
an individual to illness or modify the course of the illness
and its prognosis. The present review discusses on the advantages
of the co-treatment with melatonin and recent patents in three
major psychiatric disorders: depression, bipolar syndrome
and schizophrenia. The findings suggest new vistas in both
the pathophysiology and the pharmacology of mental disorders.
[Back to top]
Multitasking of Neuropeptide Y through the Lens of Motifs
Michael Myslobodsky
Networks controlling ingestion-related peptides are also
known to be the targets and signals for numerous other systems.
Yet, their topological properties are still ill understood.
The Ingenuity Pathway Analysis (IPA) was employed to represent
molecules engaged in feeding as nodes, and the interactions
between them as edges. Using extracted molecules as ‘seeds’
for core analysis it was possible to scrutinize some of the
complex relationships of sub-networks and the so-called ‘motifs’
well outside the neighborhoods of their classical roles. Contrary
to the requirements for modular structure, the orexigenic
and anorexigenic neuropeptides do not represent two types
of modules. They are densely interconnected. Functional annotations
showed that the same molecules are recruited ad-hoc from a
larger ‘repository’ and assembled into dynamic
networks for executing diverse physiological functions and
behaviors. Some molecules clustered in motifs appear as the
multipurpose entities for cell-to-cell signaling, organismal
development, cellular movement, growth and proliferation,
endocrine system development and tissue morphology, etc. that
apparently become active in early ontogeny. Based mostly on
neuropeptide Y (NPY), my arguments here will focus on the
potential benefits of exploring motifs in network controlling
ingestion for generating insights for polypharmacy of obesity-related
targets and co-morbid disorders. Recent patents describing
new NPY receptor antagonists directed to treat obesity and
cardiovascular disorders were cited.
[Back to top]
Recent Advancements in Anti-Migraine Drug Research:
Focus on Attempts to Decrease Neuronal Hyperexcitability
Hedvig Bölcskei, Bence Farkas, Pál
Kocsis, István Tarnawa
Migraine is a painful, sometimes debilitating disorder,
which is frequently associated with various neurological symptoms.
Its prevalence in the population is higher than that of any
other neurological disorders, thus the burden of this disease
on society is considerable. Although the introduction of triptans
nearly two decades ago revolutionized the treatment of the
disease there is still a huge unmet need regarding drugs with
better properties. Formerly, migraine therapy primarily aimed
at treating the pathological alterations of meningeal blood
vessels that are thought to directly initiate a migraine headache
attack. By now, it has been increasingly recognized by drug
companies that abnormal neural function may be more important
in the development of the disease and also in triggering an
attack. Migraine is associated with an increased neuronal
excitability and episodes of cortical spreading depression.
Understanding the molecular mechanisms underlying the abnormal
functioning of over-activated neuronal circuits may help to
identify novel anti-migraine drug targets. Besides a general
description of the pathophysiology and pharmacotherapy of
migraine this review paper aims at discussing the possible
drug targets through which migraine-related hyperexcitability
and over-excitation can be attenuated. It will be shown how
these new ideas appear in the recent patent literature.
[Back to top]
Humanin; A Defender Against Alzheimer’s
Disease?
Masaaki Matsuoka
Alzheimer’s disease (AD) is the most prevalent
neurological disease with dementia. AD-related dementia is
caused by death and dysfunction of neurons involved in cognitive
function. It has been generally believed that increased levels
of toxic amyloid-betas (Aβs)
are linked to the occurrence of neuronal death as well as
dysfunction (Aβ
cascade theory). Consequently, lowering levels of toxic Aβs
in the brain is considered to be central for therapy of AD.
Multiple drug candidates based on this therapeutic strategy
have been developed and are being vigorously developed. Some
clinical studies have indicated that this strategy is effective.
In addition to this theory, Aβ-independent
pathomechanisms have been shown to contribute to the progression
of AD-related dementia, justifying alternative strategies
for AD treatment that are effective against Aβ-independent
pathomechanisms. A possible therapeutic strategy belonging
to them is to directly suppress AD-related neuronal death
and dysfunction. A series of studies indicated that a 24-amino-acid
bioactive peptide named Humanin was shown to inhibit neuronal
cell death induced by enforced expression of familial AD-related
genes. Humanin also protected neurons from being killed by
toxic Aβs
in vitro. In addition, neuronal dysfunction-associated dementia
of mice caused by muscarinic receptor antagonists and intracranially
injected toxic Aβs
was ameliorated by Humanin therapy. Multiple studies have
indicated the existence of a putative specific Humanin receptor
on the cell membrane. These results together suggest that
an endogenous AD-related humoral factor(s) may inhibit the
progression of AD-related dementia by inhibiting both neuronal
cell death and dysfunction in vivo. Malfunction of this self-defense
mechanism is also hypothesized to be another etiology or an
aggravator of AD. Moreover, from a standpoint of AD therapy,
stimulation of the AD defense mechanism by a potent Humanin
derivative is a promising alternative strategy for AD treatment.
The present patents cover Humanin and the methods of its clinical
usage.
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