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Printable Handouts
Navigable Slide Index
- Introduction
- Use of mind-altering substances in history
- 20th Century: neuropharmacology
- Outline
- Target selection
- Targeting synapses for CNS drug treatment
- Two types of receptors
- Drug-binding sites at ionotropic receptors
- Interactions between receptors and ligands (1)
- Interactions between receptors and ligands (2)
- Complexity of synaptic mechanisms
- Detecting receptor binding in living human brain
- EEG signals as translational biomarkers
- Effect of mGlu5R inhibition on fragile X syndrome
- Discovery of a7 nAChR ligands
- Main steps in drug discovery
- All starts with a discovery phase
- Creation of an a7 nAChR HTS drug target
- High fidelity cell-based HTS assay
- a7 nAChR lead optimization funnel
- Characterization of a7 nAChR agonists
- PNU-282987 enhances synaptic transmission
- Activation and desensitization
- PHA-522121 produces a long desensitized state
- Endophenotypes
- Auditory gating impairment and schizophrenia
- a7 nAChR agonists and restoring auditory gating
- Positive allosteric modulators of a7 nAChRs
- Prototype of a7 nAChR PAMs: PNU-120596
- Type-I and Type-II PAMs
- A Type-II PAM improves auditory gating deficits
- A Type-I PAM reverses auditory gating deficits
- Temperature-dependent allosteric modulation
- When an agonist turns out to be a PAM
- PHA-568487 enhances & inhibits receptor activity
- Complexity of receptor activation
- Academia–pharma collaborations (obstacles)
- Academia–pharma collaborations (critical steps)
- Recent developments indicating a new era
- Partnership between academia and pharma
- Acknowledgements
Topics Covered
- Drug-target selection
- Synaptic targets for CNS treatments: Receptors/ion-channels
- drug binding at receptors
- Drug discovery process
- Discovery of selective ligands of nicotinic a7 receptors
- Current developments in drug discovery
Links
Series:
- Drug Discovery and Development in the Neurosciences
- Synapses, Neurotransmitters and Receptor Channels
Categories:
Therapeutic Areas:
Talk Citation
Hajos, M. (2014, April 2). Receptor-channel research at the interface between academia and pharma [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 21, 2024, from https://doi.org/10.69645/QFDP1005.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Mihaly Hajos has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Neurology
Transcript
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0:00
Hello, my name is Mihaly Hajos.
I am from Yale School of Medicine.
In my talk, I would like to
give you an insight to drug
discovery for neurological
and psychiatric disorders.
I will also focus on some
challenges in neuropharmacology
and how these obstacles could be
addressed by collaborative efforts
between academic and
pharmaceutical research.
0:26
Use of mind-altering
or psychoactive drugs,
mostly plants or plant products,
dates to prehistoric times.
Archaeological findings
demonstrated their use
dating back at least 10,000 years.
Some of these plants, for
their active ingredients,
are still used or abused today.
And some even have found their
way to clinical practice.
0:53
However, until very
recently, mode of actions
of these the mind-altering
plants or substances
have been totally unknown since
it was only in the 20th century
that we gained some insight to
basic mechanisms of brain function.
Nevertheless, artificial
modification of mood or sensation
by these plants clearly indicated
that even the highest level
of brain function can be
altered, also providing hope
for potential treatment
of mental disorders.
Eventually, a new
scientific discipline
was born, neuropharmacology,
studying drug effects
or neural function from molecular
to behavioral responses.
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