Pharm Neuro - Nts And Receptors

Front 1

Inhib NTs (AAs)

Back 1

GABA and glycine

Front 2

Acidic AAs (excitatory)

Back 2

Glutamate and aspartate.

Front 3

GABAa receptor

Back 3

Pentamer with alpha (where GABA binds), beta (where barbs bind) and gamma (benzos bind here) subunits. Primary GABA receptor subtype. Ionotropic. Open Cl- channel (inhibitory).

Front 4

Gaba-relevant drugs

Back 4

Benzodiazepines and barbituaties/ Alcohol too.

Front 5

Benzodiazepines

Back 5

Binds to gamma subunit of GABAa to increase alpha affininity to GABA.

Anxiolytic, sedative, anticonvulsant, muscle relaxant.

Treat anxiety, insomnia, seizures, alcohol withdrawal.

Increases freq of Cl- channel opening

Front 6

Barbituates

Back 6

Binds to beta subunit of GABAa receptor.

At low doses - decreases GABA dissociation
At high doses - Directly open Cl- channel.

Increases DURATION of Cl- channel opening.

Used for anesthesia and seizure disorders.

***when barbie is high, she opens doors and likes long duration***

Front 7

GABAb receptor

Back 7

Metabotropic (G-prot). Heterodimer with two 7-transmembrane spanning regions.
Stim opening of K+ channels (efflux), closes Ca++ channels. This leads to hyperpolarization.

Benzos and barbs don't bind it.

Baclofen is a GABAb agonist.

Front 8

GABAc

Back 8

Sim to GABAa. GABA much more potent to GABAc than GABAa.

Ionotropic - open Cl- channels.
High exp in retina, spinal cord, pituitary.

Not mod by baclofen, barbs or benzos.

Front 9

Glutamate

Back 9

Major role in synaptic plasticity and learning/memory.
Excess can lead to excitotoxicity.

In Alzheimers or ALS - Astrocytes don't take up excess glutamate in the synaptic cleft.

Front 10

NMDA receptor

Back 10

Glutamate. Ionotropic

Perm to calcium, Na, K.

Mg++ plugs it.

Involved in excitotoxicty. Deficiency here may lead to schizophrenia.

Front 11

AMPA/Kainate receptor

Back 11

Glutamate. Ionotropic

Front 12

Metabotropic Glutamate Receptors

Back 12

Groups I, II, III.
Signal via G prot to change PLC/Ca++ or adenyl cyclase.
Involved in memory.

Front 13

Memantine

Back 13

Low-moderate affinity NMDA antagonist.

Selectively blocks excitotoxic effects.This leads to decreased neuronal death in alzheimers.

SE: confusion, agitation, restlessness.

Front 14

Acetylcholine

Back 14

Nicotinic receptors (Muscle and neuronal) - fast excitation.

Muscarinic receptors (M1-M5). M1 most abun in brain. Slower excitation.

Brainstem has only muscarinic receptors while most of brain has both muscarinic and nicotinic.

Front 15

Ach synthesis

Back 15

Choline plus acetyl coa brough together via choline acetyl transferase. Coa is a byproduct in the synthesis of acetylcholine in this reaction.

Front 16

Nicotinic receptors

Back 16

Na++ influx. Nicotine is the major ligand.

Ionotropic

Front 17

Nicotine

Back 17

Increases alertness, reduces anxiety, relaxes muscles and promotes analgesia.

Front 18

Muscarinic receptors

Back 18

Slow excitation via increase in Ca++ which blocks K+ efflux.

Metabotropic

Front 19

M1 receptors

Back 19

Important in cognition. Atropine is an antagonist and causes delirium.

Decreased transmission in Alzheimer's.

Agonists are a potential tx for AD treatment.

Front 20

Alzheimer's disease

Back 20

Reduction in cholinergic neurons in subcortical areas of the brain.

Decreased activity in choline acetyl transferase (CAT) so there is less ACh available for neuronal transport.

Front 21

Monoamines

Back 21

DA, NE, serotonin

Made from AAs, monoamine transporters reuptake (powerful drug targets) and monoamine oxidases or Catechol-O-methyl transferases degrade.

Front 22

Dopamine

Back 22

Made from L-tyrosine.
Reuptake by dopamine transporter.

Activates receptors D1-D5.
Produced by ventral tegmental area and substantia nigra.

Inv in behavior, cognition, motor activity, motivation, reward and addiction.

Front 23

Dopamine synth

Back 23

L-tyrosine to DOPA via tyrosine hydroxylast. Dopa to dopamine via DOPA decarboxylase.

Front 24

Dopamine receptors

Back 24

All metabotropic

D1 family (D1, D5) increases adenylyl cyclase and produces excitatory response

D2 family (D2,3,4) increases phosphodiesterase to decrease cAMP and produces inhibitory response.

Front 25

4 DA pathways

Back 25

Nigrostriatal (dec in Parkinson's), mesolimbic (inc in schizo), mesocortical (dec in schizo), tuberoinfundibular.

Front 26

Dopamine disease

Back 26

Parkinson's (degradation of nigrostriatal pathway)

Schizophrenia (overactivity of mesolimbic and underactivity of mesocortical pathways)

Drug addiction - DA receptor de-sensitization.

Front 27

Dopamine and drugs

Back 27

Parkinson's tx

Antipsychotics (D2 rec antag)

Cocaine (prev reuptake)

Amphetamines (induces DA release)

Front 28

NE

Back 28

made from L-tyrosine via dopamine.

Reuptake by norepinephrine transporter

Activates alpha and beta adrenergic receptors.

Produced by locus coeruleus and caudal raphe nucleus.

Involved in depression, attention, focus, phobias, and pain.

Front 29

NE synthesis

Back 29

L-tyrosine to DOPA via tyrosine hydroxylase, DOPA to Dopamine via DOPA decarboxylase, dopamine to NE via Dopamine B hydroxylase.

Front 30

NE drugs

Back 30

Tricyclics
NE selective reuptake inhibitors
Clonidine (pain, ADHD, Tourette's, opioid detox)
Amphetamines (ADHD)
Cocaine

Front 31

Serotonin

Back 31

Made from L-tryptophan
Degraded by MAO. NOT COMT LIKE THE OTHERS.
Reuptake by serotonin transporter.
Activates 5-HT 1-7 receptors. (there are almost 15 receptors though!)
Produced by raphe nucleus.
Involved in anger, aggression, mood, sleep, sexuality, appetite, pain.

Front 32

Histamine

Back 32

H1-H4 receptors.
H1 important for arousal (inhib K channels)

Front 33

Adenosine

Back 33

Increase cAMP, receptor blocked by caffeine.

Critical signaling molecule for glial-neuronal transmission (ATP as well)

Has an inhibitory effect on CNS

Front 34

A(2A) antagonists

Back 34

ADENOSINE/ATP

may be helpful in Parkinson's. They have an inverse relationship with DA.

Front 35

P(2x) and P(2y)

Back 35

ADENOSINE/ATP

Purine receptors that are activated by ATP. ATP is released from astrocytes and accom by glutamate release.

Front 36

Cannabinoids

Back 36

THC affects brain by activating CB1 receptor. Anandamide is an endogenous CB1 ligand.

Affect memory, cognition, weight and pain perception.

Cannabinoids are rapidly synth in response to depol and can function as retrograde synaptic messengers.

Also a CB2 receptor that has less of an analgesic effect.

Front 37

Endogenous opioids

Back 37

Runners high.

Examples are endorphines, enkephalins, dynorphins.

Bind to opioid receptors (mu, delta and kappa)

The peptides are involved in opioid dependence/drug abuse, antidepressant activity and chronic pain.

Front 38

Non-competitive NMDA-receptor antagonists

Back 38

PCP, ketamine, memantine, MK-801, dextrorphan