Research Publications - College of Medicine and Health Science

Neurodegenerative Diseases
Novel Selective Ligands for Muscarinic Acetylcholine
Receptors
Five muscarinic acetylcholine receptor subtypes
(M 1 - M 5 ) have been cloned and are found in the
brain. However, the pharmacological identification
of the subtypes responsible for the various
central effects of the muscarinic drugs is difficult
due to the lack of highly selective muscarinic
agonists and antagonists. We have isolated
muscarinic M 1 and M 4 receptor subtype selective
toxins from mamba snake (Dendroaspis)
venoms. At present the status of M 1 and M 4 receptors
in health and disease states in humans
are being investigated. Our results show significant
decrease of M 4 , but not of M 1 receptors in
the hippocampus of Alzheimer’s patients compared
to controls. Moreover, changes in these
receptors in adrenalectomized animal models
which have been shown to have a selective loss
of hippocampal neurons. Attempts to isolate
and characterize M 2 , M 3 , and M 5 selective toxins
is also in progress. Behavioral, biochemical and
electrophysiological techniques are also used in
understanding the role of other neurotransmitters
in diabetes, epilepsy, aggressive behavior,
aging, and degenerative diseases.
Prof. MY Hasan
Neuroscience
The main line of research has been focusing
on neurotransmission. We have been applying
behavioral, biochemical and electrophysiological
and morphological techniques
in understanding the role of neurotransmitters
in various disorders (diabetes, epilepsy, aging,
neurodegenerative diseases). Findings indicated
significant modification of specific neurotransmitters
in many of the disorders. It appears that
alteration in calcium mobilization and free radical
system may be a common factor accounting
for some of the changes observed in aging,
diabetes and Parkinson’s disease. Another line
of research has been toxicological studies and
impact of toxins on muscle the nervous system.
We have investigated the effects of heavy
metal Intoxication in relation to degenerative
diseases. We studied impact of heavy metal
toxicity on nervous system and muscle and
observed that free radicals may be involved in
metal toxicity and antioxidants like ascorbic
acid & alpha-tocopherol may have a protective
role against metals effects Also we have been
looking and neurotoxicity and general toxicity
from organophosphates and nerve gases. We
have been screening antidotes for organophosphate
poisoning and implication for treating
exposure to nerve gas agents. Furthermore
my interest covered broad areas in medical
education and community health. Some of the
projects performed included; drug utilization
and rational use of antibiotics and analgesics in
health care centers and community, developing
Sickness Impact Profile for studying quality
of life in infertile patients, studying views of
medical students and physicians of clinical skills
teaching at the medical colleges and surveying
patient’s attitudes towards students involvement
in medical practice.
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Gastroenterology: Gastrointestinal diseases
have increased in recent years. Work stress,
alcohol, non-steroidal anti-inflammatory drugs
(NSAIDS) strong tea or coffees have contributed
to the pathology. Our research is based on
gastrointestinal secretion and the mechanism
of action of PPIs and other acid inhibitors on
acid secretion. In the early years, Histamine H2receptor
antagonist, Sucralfate and Muscarinic
receptor antagonists were used more often.
But with the introduction of the proton pump
inhibitors (PPIs) their use has declined owing to
the potent anti-secretory and anti-ulcer activity
of the PPIs. Recently we published the work
on new proton pump inhibitor, esomeprazole,
Astra-Zeneca (accepted for publication (2008)).
At present we are studying the interactions of
Aspirin in combination with ibuprofen on Gastric
acid and Ulcer formation in the rat in vivo
and in vitro (manuscript in preparation). In the
near future we are planning to study the effect
of stress on the mucosa of FSL and FRL rats and
the healing rate of alcohol-and indomethacininduced
ulcers in the same rats.
Teratology: Epilepsy affects approximately 1% of
the world’s population and it is the second most
common neurologic disorder after stroke. It is a
heterogeneous symptom complex—a chronic
disorder characterized by chronic seizures. Approximately
0.5% of all pregnancies occur in
women with epilepsy. It is known that epileptic
women demonstrate a higher liability to obstetric
complication than non-epileptic females and
congenital malformations are more common in
their offsprings than those of normal or rats.
Department of Pharmacology
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