Week 10: Inhalants and Other Depressants

Question 1

Gamma-hydroxybutyrate (GHB)

Answer 1

• Drug and neurotransmitter
• Powerful CNS depressant
• Placed in drinks
• A.k.a. “heaven”/”liquid E”
• Effects similar to ethanol

Question 2

Natural synthesis of GHB

Answer 2

• GHB can be synthesized from GABA and vice versa
• GABA -> (GABA transaminase) -> Succinic semialdehyde (SSA) -> (SSA reductase) -> GHB

Question 3

GHB Pro Drug Synthesis

Answer 3

1,4-butanediol -> (Alcohol dehydrogenase) -> Gamma-hydroxy butyraldehyde (GLB) -> (Aldehyde dehydrogenase) -> Gamma-hydroxybutyrate (GHB)

Question 4

GHB elimination

Answer 4

• Peak in blood: 15-45 mins
• Pharmacological effects start after 15-20 mins and last for 2 hrs
• Half-life: 30 mins
• Detectable in blood for 4-8 hrs and 8-12 hrs in urine

Question 5

GABA neurons release both ___ and ____

Answer 5

GABA and GHB

Question 6

Family of GHB receptors exist in brain which possesses _____ properties

Answer 6

• Hyperpolarizing
• G-protein-couple receptor that causes inhibitory effects on neuron (similar to GABA)

Question 7

GHB binding sites

Answer 7

• Agonist for GHB inhibitory receptor
• Weak agonist for inhibitory GABABb receptor

Question 8

GHB receptor localization

Answer 8

• GHB expressed in hippocampus cand cortex = depression in the NS (like alcohol)

Question 9

Subjective effects of GHB

Answer 9

45 MINS
- Stimulated, amphetamine-like, greater energy, enjoy drug effects

1.5 HRS
- Drunk, dizzy, drowsy, confused, sedated, anterograde amnesia, loss of consciousness

Question 10

How does GHB produce effects similar to deep sleep stages?

Answer 10

Produces slow wave bursts characteristic of delta and theta waves

Question 11

Drug-discrimination procedures

Answer 11

• Ability to determine similarities among subjective effects of different drugs
• Provide important info on the receptor actions for depressant drugs

Question 12

Drug-discrimination procedures for GHB

Answer 12

• Rats could differentiate between GHB and ethanol by pressing their respective levers
• Act on diff areas/pathways in the brain
• Did not press GHB lever with drugs that aren’t similar to GHB (ex. Benzodiazepine)

Question 13

GHB withdrawal

Answer 13

• Insomnia, anxiety, tremor, acute delirium
• Onset: 1-6 hrs
• Duration: 3-21 days
• Main treatment: Supportive care and benzos for control of delirium

Question 14

Amyl nitrite

Answer 14

• Inhalant drug
• Provide feelings of warmth, throbbing, light-headedness and enhanced sexual experiences
• Ex. nitrous oxide (laughing gas), volatile alkyl nitrites, nitrous oxide, volatile solvents, fuels, anesthetics

Question 15

Toulene

Answer 15

• Most common compound in inhalants
• Depressent on CNS
• Antagonist of NMDA receptor, eliminating flow of ions through NMDA channels (prevent glutamate binding) & positive modulator of GABAa receptor (increases activation) (like alcohol) = increase in NMDA receptors and decreases activation of GABAa receptors after repeated use (b/c of homeostasis)
• Binds to its own site
• Almost entirely made of carbon and hydrogen

Question 16

Absorption and elimination of inhalants

Answer 16

• Absorption: sniffing, huffing, bagging
• Most inhalants are highly lipid soluble
• Rapid absorption, rapid elimination
• Peak lvls: ~1-3 mins
• Half-life ~20 mins

Question 17

Drug-discrimination procedures of toluene

Answer 17

• Elicited amphetamine-linked lever-pressing behaviour

Question 18

Toluene seems to ____ dopamine levels

Answer 18

• Increase
• More released in VTA

Question 19

Stages of inhalant effects

Answer 19

1. Stimulant-like positive subj. effects (ex. euphoria)
2. Behavioural effects resembling alcohol intoxication
3. Enhanced depressant effects on CNS
4. Overdose

(GABAa receptors may be responsible b/c of positive modulation)

Question 20

What happens after chronic heavy use of inhalants?

Answer 20

• Sever neural damage (degrade myelin sheaths)
• Results in lower brain activity