Download presentation
Presentation is loading. Please wait.
Published byRandall Parker Modified over 9 years ago
2
some controversy……..
4
Muscarinic agonists – Muscarine
6
some controversy…….. Muscarinic agonists – Muscarine Muscarinic antagonists Synthetic and natural-
8
DA – dopamine NE – norepinephrine 5HT - serotonin
9
CNS - reward, movement, motivated behaviors, executive function? numerous DA pathways in CNS of importance for psychotropics…..
10
DA receptor subtypes ◦ 2 major families – D1 and D2 families
11
In CNS- arousal; role in depression, possible role in spinal analgesia, possible motivated behaviors such as hunger, thirst, sex, anxiety, attention? NE is in both the CNS and PNS
12
receptor subtypes ◦ alpha 1 and 2; β 1 – 3
13
Catecholamines removed by reuptake: ◦ DAT – DA transporter ◦ NET – NE transporter
14
metabolism – ◦ far slower than ACh by AChE
15
metabolism – ◦ far slower than ACh by AChE ◦ MAO enzymes (monoamine oxidase)
16
metabolism – ◦ far slower than ACh by AChE ◦ MAO enzymes (monoamine oxidase) MAOA AND MAOB enzymes MAO A – more selective for NE and 5HT
17
metabolism – ◦ far slower than ACh by AChE ◦ MAO enzymes (monoamine oxidase) MAOA AND MAOB enzymes MAO A – more selective for NE and 5HT MAO B- more selective for DA
18
Major metabolites: ◦ Important when trying to study potential differences ◦ DA - dopac and HVA ◦ NE - MHPG -(3-methoxy-4-hydroxy- phenethyleneglycol)
19
Tyrosine Tyrosine hydroxylase (rate limiting step) TH DOPA DA- β -hydroxylase Dopamine (DA) Norepinephrine (NE) Epinephrine (E) Aromatic acid decarboxylase mao homovanillic acid (HVA) pnmt catecholamines MHPG mao
20
more recent in our history of studying NT similarity to LSD found early in high concentrations in the gut found in many non neuronal cells (only ~ 1 – 2% of 5HT in whole body is in brain) cannot cross bbb so……
21
behavioral role (CNS): sleep, aggressive behavior abnormal function implicated in: ◦ schizophrenia, depression, phobic disorders, OCD, eating disorders, migraine, etc
22
synthesis ◦ amino acid precursor – tryptophan
24
synthesis ◦ amino acid precursor – tryptophan ◦ elimination of dietary tryptophan can significantly lower brain 5HT levels
25
synthesis ◦ amino acid precursor – tryptophan ◦ elimination of dietary tryptophan can significantly lower brain 5HT levels ◦ foods high in tryptophan; nuts (ie walnuts, almonds), tofu, milk, eggs, certain cheeses, turkey, seafood, seeds
26
receptor subtypes- many – at least 18 subtypes have been identified - probably best way to group 5HT1 and 5HT2 families; - some are metabotropic; some ionotropic
27
reuptake main mechanism for terminating ◦ SSRIs breakdown – major metabolite 5HIAA
28
pervasive throughout the brain classified into 2 general categories ◦ excitatory (glutamate, aspartate) ◦ inhibitory (GABA, glycine) amino acids are more difficult to classify as nt
29
first identified in leg of lobster causes hyperpolarization of neurons highest concentrations in brain and spinal cord and virtually absent in peripheral nerve or other organs does not cross bbb easily
30
stored in synaptic vesicles (like other nt) usually removed from synapse via transporter (GAT) GABA also found in glia receptor subtypes: ◦ GABA A – ionotropic – clinically important ◦ GABA B - metabotropic
31
mediates anxiolytic, sedative, anticonvulsant, muscle-relaxant and amnesic activity subunit compositions appear to vary from one brain region to another and even between neurons within a given region linked to chloride channel
33
modulatory effects
34
found in high concentrations in brain serves many functions GAD (enzyme – can convert glutamate to GABA)
36
found in high concentrations in brain serves many functions GAD (enzyme – can convert glutamate to GABA) receptor subtypes: ◦ tremendous work done in recent years
38
receptor subtypes: ◦ NMDA, ionotropic, various other receptors including metabotropic GLU R (mGLUR) ◦ families within these ◦ role of neuromodulators current potential interests ◦ reducing neurotoxicity, psychiatric disorders, substance use disorders, Alzhemiers Disease?
39
2005 – first non AChE inhibitor for treating AD Only approved for advanced (not early stage) uncompetitive low-to-moderate affinity NMDA receptor antagonist Multiple other uses possible
40
◦ acts as a neurotransmitter; also released during immune response; also found in gut ◦ antihistaminergic effects: drowsiness, dry mouth, dizziness, sleepiness, upset stomach, decreased coordination, fatigue, weight gain, dry mouth and throat, upset stomach, fluttery heartbeat, loss of appetite, hives, sleepiness, vision problems
41
Overview of nervous system
43
PNS - peripheral nervous system 2 components- autonomic and somatic 1. autonomic nervous system -“involuntary” - role in emotion and stress - controls smooth muscles, cardiac muscles and glands
44
1. Sympathetic NS “fight or flight” activated during emergencies, stress and/or arousal
46
Maintain homeostasis, energy restoration ◦ physiological changes:
48
voluntary nervous system ◦ sensory and motor nerves ◦ connection between all motor nerves and muscle (NMJ – neuromuscular junction) are nicotinic ACh synapses
50
CNS – Central Nervous System ◦ brain, spinal cord PNS – Peripheral Nervous System ◦ Somatic, autonomic
51
3 main divisions of brain ◦ hindbrain; midbrain; forebrain
52
hindbrain Medulla
53
medulla ◦ Contains part of the reticular formation – (nuclei involved in integration of information from senses, attention, arousal, and control of sleep and wakefulness)
54
medulla ◦ Contains part of the reticular formation – (nuclei involved in integration of information from senses, attention, arousal, and control of sleep and wakefulness) as well as ◦ Nuclei important for vital functions
55
medulla ◦ Contains part of the reticular formation – (nuclei involved in integration of information from senses, attention, arousal, and control of sleep and wakefulness) as well as ◦ Nuclei important for vital functions ◦ Various ascending and descending pathways
56
medulla hindbrain
57
pons ◦ Contains part of the reticular formation Nuclei important for sleep and arousal
58
pons ◦ Contains part of the reticular formation Nuclei important for sleep and arousal ◦ Specific nuclei include Raphe (5HT) – sleep and dreaming Locus coerulus (NE) - arousal
59
pons ◦ Contains part of the reticular formation Nuclei important for sleep and arousal ◦ Specific nuclei include Raphe (5HT) – sleep and dreaming Locus coerulus (NE) - arousal Cerebellum
60
Sensory information ◦ reticular formation movement ◦ substantia nigra -
61
cortical and subcortical structures
62
frontal parietal temporal occipital
63
Frontal ◦ Motor function ◦ Prefrontal – higher “executive function”
64
Frontal ◦ Motor function Prefrontal – higher “executive function” Parietal ◦ Somatosensory function Temporal ◦ Audition ◦ emotion Occipital ◦ vision
65
Prefrontal cortex
68
thalamus
69
The thalamus communicates with much of the cerebral cortex - serving as a sensory and motor information relay.
70
thalamus hypothalamus
71
thalamus hypothalamus limbic system
73
thalamus hypothalamus limbic system basal ganglia
78
Mesolimbic/cortical – ◦ Involved in reward, possible role in schizophrenia Projects to nucleus accumbens and parts of the limbic system nigrostriatal – ◦ Important in initiation of movement; system that degenerates in Parkinsons disease projections from the substantia nigra to the basal ganglia tuberofundibular – ◦ Important for hormonal release via hypothalamus and pituitary gland
81
Peptides Opioids ◦ Mu ◦ Delta ◦ Kappa ◦ Endorphins and enkephalins are opioids Substance P
Similar presentations
© 2025 SlidePlayer.com. Inc.
All rights reserved.