Biochem of Neuropsychiatric Disorders Part 1-3 Flashcards
(75 cards)
1
Q
D1 and D5 receptors?
A
Excitatory - increase cAMP
2
Q
D2, D3, D4 receptors?
A
Inhibitory - decrease cAMP
3
Q
5-HT1 and 5-HT5 receptors?
A
Inhibitory - decrease cAMP
4
Q
5-HT2 receptor?
A
Excitatory - increases IP3 and DAG
5
Q
5-HT3 receptor?
A
Excitatory - ligand gated Na+ channel
6
Q
5-HT4, 5-HT6, and 5-HT7 receptors?
A
Excitatory - increases cAMP
7
Q
Alpha1 receptor?
A
Excitatory - increases IP3 and DAG. NE > E. Smooth muscle contraction and glucose release from liver
8
Q
Alpha 2 receptor?
A
Inhibitory - decreases cAMP. E > NE. Inhibits insulin release, activates glucagon, presynaptic autoreceptors.
9
Q
Beta1, beta2, and beta3 receptors?
A
Excitatory - increases cAMP
10
Q
H1 receptor?
A
Excitatory - increases IP3 and DAG
11
Q
H2 receptor?
A
Excitatory - increases cAMP
12
Q
H3 receptor?
A
Inhibitory - decreases cAMP
13
Q
N1 and N2 receptors?
A
Excitatory - ligand gated Na+ channel
14
Q
M1, M3, M5 receptors?
A
Excitatory - increases IP3 and DAG
15
Q
M2 and M4 receptors?
A
Inhibitory - decrease cAMP
16
Q
Glutamate receptors include?
A
AMPA and Kainate, NMDA, mGluR (1-8)
17
Q
AMPA and Kainate receptors?
A
Excitatory - Na+ channels
18
Q
NMDA receptor?
A
Excitatory - Na+ and Ca2+ channels
19
Q
mGluR1, mGlurR5 receptors?
A
Excitatory - increase IP3 and DAG
20
Q
mGluR (2, 3, 4, 6, 7, 8)
A
Inhibitory - decreases cAMP
21
Q
GABAa receptor?
A
Inhibitory - ligand gated chloride channel
22
Q
GABAb receptor?
A
Inhibitory - second messenger triggered K+ channel
23
Q
GABAc receptor?
A
Inhibitory - ligand gated Cl- channel
24
Q
Glycine receptors?
A
Mostly in spinal cord. Inhibitory - ligand gated Cl- channel. Responds to Gly, but also responds to B-alanine, Ala, Pro, Ser, and taurine
25
Parkinson's disease Sx?
Tremors, bradykinesia, rigidity, postural instability, shuffling gait. Alzheimer's commonly coexists with PD.
26
Biochemical defect in Parkinson's?
Presence of Lewy bodies (eosinophilic inclusion bodies filled with neurofilaments, glycoproteins, ubiquitin, and alpha-synuclein). Loss of Substantia Nigra cells (which normally produce DA)
27
DA: Location of cell bodies, targets, receptors, and functions?
Location of cell bodies: Midbrain- specifically substantia nigra pars compacta and ventral tegmental area
Targets: Striatum (caudate and putamen), limbic cortex, amygdala, nucleus accumbens, prefrontal cortex
Receptors: D1-5
Fxns: Movement, initiative, working memory
28
DA pathways damaged in Parkinson's?
Mesostriatal (nigrostriatal) is the main pathway due to death of the substantia nigra compacta cells. Mesocortical damage can cause some of the cognitive Sx of Parkinson's
29
Mesostriatal (nigrostriatal) pathway?
Substantia nigra pars compacta to the caudate and putamen (together the striatum). Responsible for movement initiation.
30
Mesolimbic pathway?
Ventral tegmental area to the limbic system (including amygdala, cingulate cortex, medial orbital frontal cortex, hippocampus and parahippocampal gyrus, and nucleus accumbens).
31
What pathways are over-activated in Schizophrenia?
Mesolimbic (mesolimbic cortical dementia) and Mesocortical (Negative symptoms of schizophrenia)
32
Mesocortical pathway?
Ventral tegmental area to the prefrontal cortex and entorhinal cortex. Responsible for working memory, attention, and motor initiation.
33
Local DA circuits in the brain?
Retina, olfactory bulbs, hypothalamus, and medulla
34
DA synthesis?
Phenylalanine is converted to L-tyrosine by Phe hydroxylase. L-tyrosine is converted to L-Dopa by tyrosine hydroxylase. L-Dopa is converted to Dopamine by Dopa decarboxylase.
35
Main treatment for Parkinson's?
L-dopa given with carbidopa - DA does not cross the BBB, but L-dopa does. Carbidopa blocks the conversion of L-dopa to DA outside the brain.
36
Recerpine: what it's used for and significance in reference to DA?
Used to treat HTN and sometimes psychosis. DA vesicle uptake inhibitor - causes the decreased storage of DA. This can result in Parkinsonian Sx.
37
Major pathway for the breakdown of DA?
DA converted to DOPAL by MOA-B. DOPAL converted to DOPAC by aldehyde dehydrogenase. DOPAC converted to HVA by Catechol-o-methyl transferase (COMT). HVA is transported.
38
MAO inhibitors and COMT inhibitors can be used to treat what?
Parkinson's - they prevent the breakdown of DA by MAO and COMT. Can be used in combination.
39
Drugs that block the degradation of DA?
Depreny (MAO-I), Selegiline (MAO-I), Tolacapone (COMT-I), Entancapone (COMT-I)
40
Dopamine receptor agonists can be used to treat what?
Parkisnon's. Activates the DA receptors on the post-synaptic side. Includes the drug Bromocriptine.
41
Typical antipsychotics: mechanism and side effects?
Mechanism: DA receptor antagonists.
Side effects: Parkinson-like Sx
Drugs include Chlorpromazine, Loxapine, and Haloperidol
42
Side effect of L-dopa treatment?
Hallucinations
43
Amphetamine mechanism?
Increase DA release
44
Cocaine and tri-cyclic antidepressants mechanism?
Block the reuptake of DA
45
DA-ACh balance: what is is, why is it important?
Both DA and ACh are important for basal ganglia fxn. If DA levels drop and ACh levels stay the same, it is similar to having too much ACh. Anticholinergics have some usefulness in treating Parkinson's (they predate the use of L-dopa)
46
Schizophrenia Sx?
Positive Sx: hallucinations, delusions, bizarre behavior.
| Negative Sx: social withdrawal, emotional blunting
47
Possible causes of Schizophrenia?
Genetics, structural abnormalities in medial temporal lobe (altered orientation of hippocampal pyramidal cells which affect the molecules involve in cell migration and adhesion during brain development, enlarged ventricles)
48
Serotonin: Location of cell bodies, targets, receptors, and functions?
Location of cell bodies: Midbrain and pons - raphe nuclei
Targets: entire CNS
Receptors: 5-HT (1-7)
Fxn: Mood elevation
49
Melatonin: produced where and regulates what?
Produced in pineal gland. Regulates endocrine rhythms. Antioxidant that is protective against DNA damage.
50
Seratonin and Melatonin are derived from what?
Tryptophan. Tryptopha is converted to Serotonin by tryptophan hydroxylase and Dopa decarboxylase. Serotonin is converted to Melatonin. Serotonin is also converted to 5-hydroxyindole acetic acid by MAO-A. 5-hydroxyindole acetic acid can be measured in the urine to test serotonin levels in the brain
51
Typical antipsychotics target what?
D2 receptors, and also D1, cholinergic, and histaminergic receptors as well. Tend to cause parkinsonian symptoms.
52
Atypical antipsychotics inhibit what?
5-HT2 receptors - are better tolerated despite sometimes causing parkinsonian symptoms
53
LSD mechanism?
5-HT2 agonist (opposite of an atypical antipsychotic)
54
MAO inhibitors are used for what?
Anti-depressants: prevent conversion of Serotonin to 5-hydroxyindole acetic acid
55
5-HT3 inhibitors like Ondansetron are used for what?
Nausea associated with cancer therapy
56
Selective Serotonin Reuptake inhibitors are used for what?
Anti-depressants
57
Sumatriptan is used to treat what and how does it do this?
Treats migraines by stimulating 5-HT1 (B, D, F) receptors which decreases cAMP
58
Novel anxiolytics are?
5-HT1a agonists - treat anxiety disorders
59
MT1 receptor locations?
Pars tuberalis of the pituitary gland and suprachiasmatic nuclei of the hypothalamus
60
MT2 receptor location?
Mainly in retina
61
NE: locations of cell bodies, targets, receptors, and functions?
Location of cell bodies: Pons - locus ceruleus and lateral tegmental area
Targets: entire CNS
Receptors: alpha 1 and 2, beta 1, 2, 3
Functions: alertness, mood elevation
62
NE and Epi synthesis?
Tyrosine converted to L-dopa by tyrosine hydroxylase. L-dopa converted to DA by Dopa decarboxylase (requires vitamin B6 and the drug a-methyldopa inhibits dopa decarboxylase). DA is converted to NE by dopamine beta-hydroxylase (requires vitamin C). NE is converted to Epi by phenylethanol amine N-methyl-transferase (induced by glucocorticoids as part of the Epi stress response and requires SAM as a cofactor)
63
Epi and NE are degraded by MAO into what?
MA (dihydroxymandelic acid) which is further degraded by COMT to VMA
64
Epi is degraded by COMT into what?
Met (metanephrine) which is further degraded by MAO to VMA
65
NE is degraded by COMT into what?
NM (normetanephrine) which is further degraded into VMA
66
Metanephrines and vanillylmandelic acid (VMA) are diagnostic for what?
Adrenal tumors (pheochromocytomas)
67
Beta1 receptor?
Excitatory - increases cAMP. E = NE. Cardiac.
68
Beta2 receptor?
Excitatory - increases cAMP. E >> NE. Wide sympathetic activity, including bronchi.
69
Beta3 receptor?
Excitatory - increases cAMP. NE > E. Lypolysis in adipose tissue.
70
Histamine: Location of cell bodies, targets, receptors, and functions?
Location of cell bodies: Hypothalamus - tuberomammilary nucleus. Midbrain - reticular formation.
Targets: entire brain
Receptors: H (1-4)
Functions: Alertness
71
Histamine is synthesized from what?
Histidine by histidine decarboxylase.
72
Anti-histamines to treat allergies are what?
H1 blockers. Also hit H1 receptors in the brain which causes sedation. Newer H1 antihistamines have a lower penetration of the BBB to get rid of that side effect.
73
H2 blockers are used for what?
Block release of acid in the stomach. Do not cross BBB well.
74
H3 receptors are what?
Primarily presynaptic autoreceptors, and may act as presynaptic inhibitory receptors on DA, GABA, ACh, NE, and serotonin neurons. Found in bone marrow and WBCs
75
H4 receptors are found where?
Primarily bone marrow and WBCs
