GABA and Glycine: recap

1
GABA and Glycine recap

• Inhibitory neurotransmitters
• Synthesis and packaging into vesicles.
• Removal from synapse
• Date-rape drug gamma-hydroxybutyrate (GHB) or
• flunitrazepam (Rohypnol)
• GABA receptors
• Benzodiazepines (Valium, Xanax, Ativan)
• Glycine

Excitatory actions of GABA
in the developing brain. Box 6D OMIT all of
BOX 6D
2
Figure 6.1 Examples of small-molecule and
peptide neurotransmitters (Part 2)
3
Figure 6.8 Synthesis, release, and reuptake of
the inhibitory neurotransmitters GABA and glycine
(Part 1)
GABA
Fig. 6.8 (A)
4
Figure 6.8 Synthesis, release, and reuptake of
the inhibitory neurotransmitters GABA and glycine
(Part 2)
GLYCINE
Fig. 6.8 (B)
5
Figure 6.9 Ionotropic GABA receptors
Fig. 6.9
6
Figure 6.1 Examples of small-molecule and
peptide neurotransmitters (Part 4)
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Chapter 6 NEUROTRANSMITTERS AND THEIR
RECEPTORS

• CHAPTER 6
• Part II
• Biogenic amines and psychiatric
• disorders.
• Addiction
• Purine neurotransmitters
• Peptide neurotransmitters
• Unconventional neurotransmitters
• Marijuana and the brain

8
Figure 6.10 The biosynthetic pathway for the
catecholamine neurotransmitters
Tyrosine
Precursor
DOPA
DOPAMINE
Neurotransmitters
Norepinephrine
Fig. 6.10
Epinephrine
9
Figure 6.11 The distribution of catecholamine
neurotransmitters in the human brain
Parkinsons Disease affects dopaminergic neurons
of the substantia nigra
Fig. 6.11
10
BOX 6F ADDICTION
Drug Addiction aka substance dependence compu
lsive drug use occurs despite the negative
consequences for the afflicted individual
(NeuroScience text) is a user's compulsive need
to use drugs in order to function normally. When
such substances are unobtainable, the user
suffers from withdrawal. (Wikipedia) physi
cal and psychological dependence in which the
individual continues the drug-taking behavior
despite maladaptive consequences (American
Psychiatric Association www.psych.org )
Cocaine- midbrain region of brainstem (ventral
tegmental area) Heroin- same dopaminergic
circuitry as cocaine (vta)
11
B0X 6E BIOGENIC AMINE NEUROTRANSMITTERS
AND PSYCHIATRIC DISORDERS

• Psychotropic drugs
• drugs that altar behavior, mood or
  perception
• Anti-psychotics ie. Reserpine (1950s), Haldol
  (haloperidol)
• Risperdal (risperdal)
• Anti-anxiety ie. MAO inhibitors, benzodiazepines
• Librium
  (chlordiazepoxide) , Valium (diazepam)
• XanaxTM (alprazolam) AtivanTM (lorazepam)
• 3. Anti-depressants ie.
• a. MAO inhibitors (tranylcypromine,
  phenelzine)
• b. tricyclic antidepressants (desipramine)
  or Elavil (amytripyline)
• c. SSRIs Prozac (fluoxetine), Zoloft
  (sertraline)
• Stimulants ie. Dexedrine or Adderall
  (d-amphetamine)
• MDMA (Ecstasy/Molly), Methamphetamine

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MDMA aka Ecstacy
MDMA (contracted from 3,4-methylenedioxy-methamphe
tamine) is a substituted amphetamine class of
drug that is consumed primarily for its euphoric
and empathogenic effects. Pharmacologically, MDMA
acts as a serotonin-norepinephrine-dopamine
releasing agent and reuptake inhibitor. http//en
.wikipedia.org/wiki/MDMA
13
COMBATING METHAMPHETAMINE USE
14
Figure 6.11 The distribution of DOPAMINE
neurotransmitters in the human brain (Part 1)
Fig. 6.11 (A)
15
BOX 18A PARKINSONS DISEASE

• Idiopathic Disease
• When was it first described and
• by whom?
• Typical age of onset
• Is it inherited?
• Symptoms
• Cellular and molecular defect
• Treatments/therapy

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Figure 6.11 The distribution of NOREPINEPHRINE
neurotransmitters in the human brain (Part 2)
Fig. 6.11 (B)
17
Figure 6.11 The distribution of EPINEPHRINE
neurotransmitters in the human brain
Fig. 6.11 (C)
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Figure 6.12 Metabotropic receptors for
catecholamine neurotransmitters
Fig. 6.12
19
Figure 6.12 Metabotropic receptors for
catecholamine neurotransmitters (Part 1)
Fig. 6.12 (A)
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Figure 6.12 Metabotropic receptors for
catecholamine neurotransmitters (Part 2)
Fig. 6.12 (B)
21
Figure 6.13 The distribution of histamine and
serotonin neurotransmitters in the human brain
SEROTONIN
HISTAMINE
Fig. 6.13
22
Figure 6.14 Synthesis of histamine
and serotonin
HISTAMINE
Fig. 6.14
SEROTONIN
23
Figure 6.1 Examples of small-molecule and
peptide neurotransmitters (Part 3)
24
Figure 6.15 Purinergic Receptors
Fig. 6.15
25
Figure 6.15 Purinergic Receptors (Part 1)
ATP
Fig. 6.15 (A)
26
Figure 6.15 Purinergic Receptors (Part 2)
ADENOSINE
Fig. 6.15 (B)
27
Figure 6.1 Examples of small-molecule and
peptide neurotransmitters (Part 5)
Example of an ENKEPHALIN
28
Figure 6.16 Proteolytic processing of
pre-propeptides
Fig. 6.16
29
Figure 6.17 Amino acid sequences of
neuropeptides
Substance P
hippocampus, neocortex, GI tract
Brain/Gut
Opioid
Pituitary
Hypothalamic
Misc
Fig. 6.17
30
Table 6.2 ENDOGENOUS OPIOIDS
Hydrocodone/Oxycodone narcotics that use opioid
receptors
- Side effects, abuse, withdrawal
31
Figure 6.16 Proteolytic processing of
pre-propeptides TO PRODUCE ENDORPHINS
PRE-PRO-OPIO-MELANO-CORTIN
Endorphin propeptide
Endogenous Opioid Peptide
Fig. 6.16 (A)
32
Figure 6.16 Proteolytic processing of
pre-propeptides FOR ENKEPHALINS
Fig. 6.16 (B)
33
Box 6G Marijuana and the brain
CB1-receptor for THC
Box 6G
34
Figure 6.18 Endocannabinoid signals involved
in synaptic transmission
Agonist
Antagonist
Fig. 6.18
2-AG
35
Figure 6.20 Synthesis, release, and
termination of NO
Fig. 6.20