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OREXINS
NEUROPEPTIDES
SUBHASH CHANDRA GAYAM
MSc NeuroPharmacology Student
University of East London.
Oral Presentation: Module-Lsmco-1
OREXINS
• What exactly Orexins means?
• Orexins(also called Hypocretins) are
Neuropeptides produced exclusively by a
well defined group of neurons in the
lateral hypothalamus.
TYPES OF OREXINS AND
RECEPTORS
• Orexins A &B are residue peptides,which
were recently isolated from the rat
hypothalamus.
• Orexins A & B bind to two receptors,
• Orexin1(OX1) Receptor(Ox-A)
• Orexin2(OX2) Receptor(Ox-B)
• Orexin2(OX2) Receptor(Non-selective)
STRUCTURE OF OREXIN
N-terminal
DIAGRAM OF BRAIN
corpuscollosum
Parietal lobe
frontallobe
occipitallobe
Posterior(wake)
Preopticarea(sleep)
temporallobe
posteriorlateralhypothalamus
pons
medulla Braincerebellum
stem
SELECTIVE OREXIN1RECEPTOR ANTAGONIST
• 1-(2-methyl benzoxazol-6-yl)-3(1,5)naphthyridin-4-ylurea hydrochloride.
• Orexin A(Intracerebroventricular).
• Antagonist(Peripheral administration).
• Orexin A is orexigenic in both male and
female rats.
• Selecive OX1 receptor antagonist block the
response of orexin A.
Effects of orexin-A and
Antagonist on rats(M&F)
• Dose dependent in female rats,but not the
males(figure-1).
• The response of oxA was blocked by
antagonist(figure-2)
• After an overnight fast,antagonist reduced
food intake during the first 4 hours in male
rat(figure-3).
Figure-1(Effects of orexinA dose
-dependent
Oxa(2.3nmol)
oxA(2.3nmol) oxA(7nmol)
vehicle
Figure-2(Food consumption)
Figure-3 (Food consumption)
Narcolepsy-neurodegenerative
disease of the orexin system
• Narcolepsy is characterised by excessive
daytime sleepiness(EDS),cataplexy,sleep
paralysis,hypnogogic hallucinatios and
reapid eye ovement(REM).
• Narcolepsy is associated with massive
reduction in the number of orexin cells.
• Symptoms:
• Irresistible,episodes of involuntary’naps’.
Pharmacologic treatment of
narcolepsy.
CONCLLUSION
• However,knowledge about narcolepsy often
remains limited even among neurologists.
• Life style changes are rarely sufficient to
adequately control the symptoms of
narcolepsy and therefore most patients
require life long medication to cope with
debilitating effect of excessive day time
sleepiness(EDS).