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

Figure 6.1 Examples of small-molecule and peptide neurotransmitters (Part 2)

Figure 6.8 Synthesis, release, and reuptake of the inhibitory neurotransmitters GABA and glycine (Part 1)

Fig. 6.8 (A)

GABA

Figure 6.8 Synthesis, release, and reuptake of the inhibitory neurotransmitters GABA and glycine (Part 2)

Fig. 6.8 (B)

GLYCINE

Figure 6.9 Ionotropic GABA receptors

Fig. 6.9

Figure 6.1 Examples of small-molecule and peptide neurotransmitters (Part 4)

Chapter 6 NEUROTRANSMITTERS AND THEIR RECEPTORS

CHAPTER 6Part II

• Biogenic amines and psychiatricdisorders.

• Addiction

• Purine neurotransmitters

• Peptide neurotransmitters

• Unconventional neurotransmitters

• Marijuana and the brain

Figure 6.10 The biosynthetic pathway for the catecholamine neurotransmitters

Fig. 6.10

DOPAMINE

Norepinephrine

Epinephrine

Tyrosine

DOPA

Precursor

Neurotransmitters

Figure 6.11 The distribution of catecholamine neurotransmitters in the human brain

Fig. 6.11

Parkinson’sDiseaseaffects“dopaminergic”neurons of thesubstantia nigra

BOX 6F ADDICTION

Drug Addiction aka “substance dependence”

“compulsive 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)

“physical 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)

B0X 6E BIOGENIC AMINE NEUROTRANSMITTERS AND PSYCHIATRIC DISORDERS

Psychotropic drugs: drugs that altar behavior, mood or perception

1.Anti-psychotics ie. Reserpine (1950’s), Haldol™ (haloperidol)Risperdal™ (risperdal)

2.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. SSRI’s Prozac™ (fluoxetine), Zoloft™ (sertraline)

4.Stimulants ie. Dexedrine™ or Adderall™ (d-amphetamine)

MDMA (Ecstasy/Molly), Methamphetamine

MDMA: aka Ecstacy

MDMA (contracted from 3,4-methylenedioxy-methamphetamine) “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

COMBATING METHAMPHETAMINE USE

Figure 6.11 The distribution of DOPAMINE neurotransmitters in the human brain (Part 1)

Fig. 6.11 (A)

BOX 18A PARKINSON’S 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

Figure 6.11 The distribution of NOREPINEPHRINE neurotransmitters in the human brain (Part 2)

Fig. 6.11 (B)

Figure 6.11 The distribution of EPINEPHRINE neurotransmitters in the human brain

Fig. 6.11 (C)

Figure 6.12 Metabotropic receptors for catecholamine neurotransmitters

Fig. 6.12

Figure 6.12 Metabotropic receptors for catecholamine neurotransmitters (Part 1)

Fig. 6.12 (A)

Figure 6.12 Metabotropic receptors for catecholamine neurotransmitters (Part 2)

Fig. 6.12 (B)

Figure 6.13 The distribution of histamine and serotonin neurotransmitters in the human brain

Fig. 6.13

HISTAMINE SEROTONIN

Figure 6.14 Synthesis of histamine and serotonin

Fig. 6.14

HISTAMINE

SEROTONIN

Figure 6.1 Examples of small-molecule and peptide neurotransmitters (Part 3)

Figure 6.15 Purinergic Receptors

Fig. 6.15

Figure 6.15 Purinergic Receptors (Part 1)

Fig. 6.15 (A)

ATP

Figure 6.15 Purinergic Receptors (Part 2)

Fig. 6.15 (B)

ADENOSINE

Figure 6.1 Examples of small-molecule and peptide neurotransmitters (Part 5)

Example of an ENKEPHALIN

Figure 6.16 Proteolytic processing of pre-propeptides

Fig. 6.16

Figure 6.17 Amino acid sequences of neuropeptides

Fig. 6.17

Brain/Gut

Opioid

Pituitary

Hypothalamic

Misc

Substance P hippocampus, neocortex, GI tract

Table 6.2 ENDOGENOUS OPIOIDS

Hydrocodone/Oxycodone – narcotics that use opioid receptors

- Side effects, abuse, withdrawal

Figure 6.16 Proteolytic processing of pre-propeptides TO PRODUCE ENDORPHINS

Fig. 6.16 (A)

PRE-PRO-OPIO-MELANO-CORTIN

Endogenous Opioid Peptide

Endorphin propeptide:

Figure 6.16 Proteolytic processing of pre-propeptides FOR ENKEPHALINS

Fig. 6.16 (B)

Box 6G Marijuana and the brain

Box 6GCB1-receptor for THC

Figure 6.18 Endocannabinoid signals involved in synaptic transmission

Fig. 6.18

= Agonist

= Antagonist

2-AG

Figure 6.20 Synthesis, release, and termination of NO

Fig. 6.20