1: Synaptic Drug Presentations

Bafilomycin A1

• blocks vacuole type-ATPase proton pump, preventing synaptic vesicle acidification

• neurotransmitters cannot be loaded into vesicles impairing synaptic transmission

REVERSIBLE

TAK-242 effects

• selectively inhibits toll-like receptor 4 (TLR4)

• prevents downstream co-adaptor proteins from activating NF-kB mediated production of cytokines

• reduces inflammation (innate immune)

REVERSIBLE

MG-132

• proteasome inhibition

• induces apoptosis and suppresses cell proliferation

• can reduce NF-kB down-regulating cytokine release and neuroinflammation

REVERSIBLE

IBA1/AIF1

• controls cytoskeleton and mobility

• triggers conformational change via actin filament interaction

• Microglia marker

• promotes neuroprotection and synaptic plasticity

REVERSIBLE

GFAP

• modulates astrocyte motility and shape

• Astrocyte marker

• Neuroprotective, modulates EAAT1, helps astrocytes carry out functions

  • BBB support, neurotransmitter regulation

REVERSIBLE

Pericytes

• BBB establishment and maintenance

• capillary constriction to modualte blood flow and ensure neurons obtaining nutrients

• decreases immune patrolling of CNS decreasing inflammation

• member of neurovascular unit communicating external stimuli to brain

REVERSIBLE

Conotoxin

• acts on ligand-gated ion channels, GPCRs, neurotransmitter transporters, voltage-gated ion channels

• Subtypes affect VGSC in differing ways (large part in AP)

NON-REVERSIBLE

Tetrodotoxin (TTX)

• blocks VGSC to prevent AP —> muscle paralysis

• Blocks pore, comptes with μ-conotoxin

REVERSIBLE

μ-conotoxin

inhibits VGSC by physically blocking the pore, competes with TTX

μO-conotoxin

inhibits VGSC by blocking pore loop/voltage sensors

ẟ-conotoxin

activates VGSC by binding to channel site, prolonged AP and hyperexcited neuron

Perineuronal nets

• specialized ECM surrounding soma + proximal dendrites

• stabilize synapses/receptors

• limit synaptic plasticity

• regulate excitation/inhibition

• modulate learning and memory

• neuroprotective

REVERSIBLE

Dynasore

• inhibits dynamin reducing endocytosis but protecting against oxidative stress

• blocks synaptic vesicle recycling

• disrupts lipid rafts

• prevents mitochondrial fission

REVERSIBLE

Ketamine

• non-competitive NMDA antagonist

• prevents channel opening blocking Na+ and Ca2+ (LTP/LDP)

• Alters gene expression/synaptic plasticity

NON-REVERSIBLE

quisqualate

• AMPA receptor agonist + glutamate analog

• induces EPSPs to promote Ca2+ influx and neurotransmitter release

• amino acid neuroprotection to prevent over-excitation

REVERSIBLE

Tetanus Toxin (TeNT)

• inhibits release of GABA and glycine —> no negative motor control —> constant muscle spasms

• cleaves SNARE proteins blocking neurotransmitter release

• travels via retrograde transport

REVERSIBLE

Ambien (Zolpidem)

• enhance GABA binding, positive allosteric modulator

• CNS depressant to treat insomnia

• GABA released during sleep to inhibit neurons that stimulate arousal

REVERSIBLE

Botulinum toxin

• blocks ACh release at NMJ (PNS)

• cleaves SNARE—> vesicle fusion blocked —> neurotransmitter inhibition

• flaccid paralysis

• retrograde transport

NON-REVERSIBLE

Alpha-Bungarotoxin

• competitive ACh antagonist @ NMJ

• NT block + disruption of Ca2+ release and influx

• respiratory failure, paralysis, death

NON-REVERSIBLE

Scopolamine

• muscarinic receptor antagonist blocking ACh binding

• permeates BBB (lipophilic)

• affects CNS and PNS

• prevents nausea and vomiting

REVERSIBLE

Donepezil

• Acetylcholinesterase inhibitor decreasing it’s affinity to ACh

• increases ACh transmission

• Off target decrease in Aβ plaques and tau entanglements

• Restores cognitive function in AD

REVERSIBLE

Sinemet

• increases intracerebral dopamine in SNc (paras compacta)

• L-dopa crosses BBB and converted to dopamine

• Treats early Parkinsons

REVERSIBLE

Psilocybin

• Magic mushrooms

• 5-HT2A agonist (serotonin) + acts on GPCRs

• Enhances synaptic plasticity and increases spine density

MDMA

• ecstacy

• Enters presynaptic catecholine terminals + disrupts VMAT2-mediated vesicular uptake

• accumulation of 5-HT, DA, and NE

Adderall

• increases DA, NE, and 5-HT —> inhibition of dopamine recycling DAT

• improves alertness and focus

Selegiline

• irreversible MAO-B inhibitor

• Used for PD and depression

Benadryl (diphenhydramine)

• Crosses BBB

• competitive agonist for mACh receptor + inverse agonist of H1 receptor

• suppresses nausea in PD, mitigates swelling/irritation

Lecanemab

• AD treatment

• prevents amyloid-beta interference with synaptic firing

Suvorexant

• Treats chronic insomnia

• inhibits orexin pathway, decreased neuronal firing + NT release

Isoflurane

• Positive regulator of GABA and glycine and decreses nicotininc ACh receptors

• anesthetic

Keppra (Levetiracetam)

• anticonvulsant controlling occurrence of seizures, for epilepsy

• binds to SV2A releasing GABA

Methylphenidate

• treatment of ADHD and narcolepsy

• blocks NE and DA uptake binding to DAT and NET

Fentanyl

• inhibits GABA guarding increasing DA

• binds opioid receptors and reduces neuronal excitability

Narcan (Naloxone)

• competitive opioid receptor antagonist (higher affinity than fentanyl)

• reverses respiratory arrest

Ramelteon

• chronic insomnia treatment

• Competitive GPCR agonist for M1 and M2 receptors in SCN

THC (delta-9-tetrahydrocannabinol)

• binds to CB1 and CB2 receptors (retrograde)

• inhibition of neurotransmitter release

Caffeine

• competitive adenosine receptor antagonist

• promotes arousal, alertness, and cognitive abilities

Nourianz

• Adenosine A2A receptor antagonist

• Used to treat PD during off periods (taken in conjunction with L/C)

Resveratrol (RV)

• potential AD treatment

• Strong antioxidant

• known to influence signaling pathways such as NF-kB

Pitolisant

• anti-narcoleptic drug, reduces cataplectic attacks

• increases histamine release, competitive antagonist of H3R

Sodium Oxybate (Xyrem)

• GABA_B receptor agonist

• to treat narcolepsy