Pharmcy Psych CNS Introduction 2013

8/12/2019 Pharmcy Psych CNS Introduction 2013

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Cerebral cortex Frontal lobeplanning Motor Speech Somato-sensory Association Vision, Smell, Hearing

Limbic system

Hippocampuso Memory

Amygdalao Moodo Aggression

Hypothalamuso Biological needs

Midbrain Substantia nigra

o Movement Basal ganglia

o Motivation behavioro Vision/hearing relay

Brainstem Reticular formation

o Sleep/arousal Medulla and Pons

o Breathingo Blood pressure


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Spinal Cord Connects body to brain Input of peripheral information

o Pain, position, etc. Output of central message

o Movement, blood pressure,temperature

Neurotransmission

Synthesis Packaging Release Receptors Reuptake Degradation


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Amino Acid Neurotransmitters

Excitatory Glutamate

Inhibitory GABA

***Balance is essential: Toomuch glutamateseizures, Too much GABAsedative

Conditions Related to Glutamate and/or GABA

Epilepsy Addiction Stroketoo much glutamate Schizophrenia Anxiety Sleep disorders Anesthesia

Glutamate Synthesis & Packaging


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Receptors IonotropicNa & Ca

o AMPA (primary excitatory receptor transmission)o NMDA (plasticity-> memory learning)o Kainate

Metabotropic pre and posto mGluR

Reuptake Astrocytes prevents excitatory toxicity

Recycled!o Glutamate back to glutamine


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GABA Synthesis & Packaging

GABAAreceptors IonotropicCl-transportedinto post-synaptic cell hyperpolarize less likely to fire impulse

Benzodiazepines, alcohol, barbiturates, inhalants


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GABABreceptorsMetabotropicGiCan be pre- or post-synaptic

Presynaptic on other (Glu, DA, NE, 5-HT) neurons to decrease release oftransmittersfrom those neurons


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Monoamine Neurotransmitters

Catecholamineso Dopamineo Norepinephrineo Epinephrine

Serotonin (5-HT) HistamineCatecholamines

o Synthesis of ALL catecholamines

Tyrosine Hydroxylase (TH) rate limiting enzyme in formation ofDopamine.

Degradation dont need to know the broken down metabolites Monoamine Oxidase (MAO)BOTHmonoamines and Catecholamines Intracellular (mitochondria)Extracellular (in synapse)

Catechol-O-methyl transferase (COMT)ONLYCatecholaminesExtracellular only (in synapse)Only catecholamines


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Dopamine

Cell bodies in only two places VTAmotivation, reward, and attention

o Addiction Substantia nigramotorlearning and execution

o Movement disordersParkinsons Disease Synthesis

o Rate limiting enzyme is THo If want more dopamine must give Dopa

Packaging Vesicular monoamine transporter (VMAT) ALL monoamines use the same

transporter


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Synaptic Transporter/Reuptake 1removal from synapse

Dopamine transporter (DAT) Vesicular

Vesicular monoamine transporter Degradation MAO/COMT Dopamine

MAO (intracellular and synaptic) COMT (synaptic only)

Receptors D1 Family (D1, D5)

o Coupled to Gs (s) stimulatory D2 Family (D2, D3, D4)

o Coupled to Gi/Go (i) inhibitoryo Presynaptic autoreceptorsinhibit dopamine releasenegative feedbacko Postsynaptic

Circuitry VTAproject to limbic (nucleus accumbens, amygdala, hippocampus) and cortex

o Motivated decisionsseeking reward Substantia nigraproject to dorsal striatum

o Motormovement Diseases/Conditions

Parkinsons Substance Abuse Mood disorders


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How to regulate Dopamine Synthesis

Increase Dopa VMAT

Decrease vesicular Receptors

Block D1R/D2R Degradation

Increase/decrease COMT/MOA Reuptake

Block DATNorepinephrine catecholamine

Cell bodies in only two places Locus ceruleus (LC) Brainstem

Projections to: cerebral cortex, thalamus,amygdala

Functions: sleep/wake, attention (ADHD),negative memories (fear, anxiety, PTSD),

Mood, Depression

Synthesis From DA (dopamine hydroxylase)

Vesicular Packaging VMAT

Degradation MAO (intracellular and synaptic) COMT (synaptic only)

Synaptic transporters 1removal from synapse

o NorEpinephrine Transporter (NET)o Reuptake NET


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Receptors 1/ Gq

stimulatory

2/ Gi

inhibitory

o Presynaptic autoreceptorso Postsynaptic

/Gs

stimulatory Circuitry

Locus ceruleus (LC), brainstem Projections to cortex, amygdala,

thalamus

Diseases/Conditions Cognition ADHD Depression PTSD

Epinephrine

Found in very few neurons in medulla Function: respiration regulation


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Serotonin (5-HT+)monoamine NOT catecholamine

Cell bodies primarily in raphe Several hundred thousand neurons are 5-HT+

Project to limbic forebrain, cortex, striatum and DA neurons Attention, sleep/arousal, emotion and mood

Especially depressionSynthesis

From tryptophan (tryptophan hydroxylase) Degradation

MAO(intracellular and synaptic) Transporters

Vesicularo Vesicular monoamine transporter (VMAT)

Synaptic1removalfrom synapseo Serotonin transporter (SERT)

Receptors

13 different receptors identified (12metabotropic, 1 ionotropic)

5HT1D (pre) and 1A/Gi(post)autoreceptors inhibit

o Migraine (agonists) 5HT2A/ Gq

o Antipsychotics (antagonists)excitatory

5HT3ionotropico Anti-nausea (antagonists)excitatory

Circuitry Cell bodies in cerebellum, brainstem Projections to cortex, limbic, midbrain


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Diseases/Conditions Depression Antipsychotics Migraines Obesity/Weight Loss

Acetylcholine

Cell bodies in forebrain and brainstem Interneurons in striatum

o movement Project to limbic forebrain, cortex,

striatum

Cognition, movement, reward Synthesis

From choline and acetyl CoAo Choline Acetyltransferase (ChAT)

Degradation AChE(intracellular and synaptic)

Transporters Vesicular (VT)

o Vesicular acetylcholine transporter SynapticCholine only (NOT ACh)

o Choline transporter Receptors

Muscarinico M2/Gi( pre and post)o M1/Gq(post)

Nicotinico Ionotropic


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Diseases/Conditions Alzheimers Parkinsons Antidepressants

HistamineMonoamine Synthesis

HistadineHistamine Physiological Function

Sleep/arousal Feeding Cognition

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Pharmcy Psych CNS Introduction 2013