Psychopharmacology Final

Morphine — mechanism and use

μ-opioid receptor agonist; used for pain.

Heroin — mechanism and classification

Pro-drug converted to morphine; semisynthetic; illicit.

Fentanyl — mechanism and use

Potent μ agonist; pain & anesthesia.

Carfentanil — mechanism and classification

Ultra-potent μ agonist; veterinary only.

Methadone — mechanism and use

μ agonist + NMDA effects; OUD & analgesia.

d-Methadone — mechanism and use

NMDA antagonist; investigational analgesic.

l-Methadone — mechanism and use

μ agonist; analgesia & OUD.

Oxycodone — mechanism and use

μ agonist; pain.

Naloxone — mechanism and use

Opioid antagonist; reverses overdose.

Naltrexone — mechanism and use

Long-acting antagonist; OUD/AUD.

Nalmefene — mechanism and use

Potent long-lasting antagonist; overdose & OUD.

Buprenorphine — mechanism and use

Partial μ agonist; OUD.

Suboxone — components & purpose

Buprenorphine + naloxone; prevents injection abuse.

Clonidine — mechanism and use

α2 agonist; reduces withdrawal via ↓NE.

RB-101 — mechanism

Enkephalinase inhibitor; boosts endogenous opioids.

Kratom — mechanism and use

μ agonist plant alkaloids; pain/withdrawal; dependency risk.

Movantik — mechanism and use

Peripheral μ antagonist; treats OIC.

Heroin vaccine — mechanism

Antibodies bind heroin preventing brain entry.

Electroacupuncture — effect

↑Dynorphin; blocked by naloxone.

What do opioids do at therapeutic doses?

Pain relief, relaxation, mild euphoria.

What occurs at high opioid doses?

Euphoria, reinforcement, high abuse risk.

What occurs at very high opioid doses?

Respiratory depression, low BP/temp, death.

Source of natural opioids

Opium poppy.

Morphine BBB penetration

3% crosses BBB.

Heroin BBB penetration

68% crosses BBB.

Do opioids cross placenta?

Yes → neonatal withdrawal.

Opioid metabolism/excretion

Liver metabolism; urine excretion.

Common opioid physiological effects

Constipation, miosis, ↓respiration, vomiting.

Why opioids cause vomiting

Stimulates area postrema.

Four endogenous opioid peptides

β-endorphin, enkephalins, dynorphins, nociceptin.

Genes encoding endogenous opioids

POMC, proenkephalin, prodynorphin, pronociceptin.

Enzymes breaking down endogenous opioids

Enkephalinase, endorphinase, CPA.

Mu receptor functions

Analgesia, euphoria, dependence, respiratory depression.

Delta receptor functions

Analgesia, mood regulation.

Kappa receptor functions

Dysphoria, diuresis, analgesia.

NOP-R receptor functions

Pain modulation; opposes classical opioids.

Opioid receptors are what type?

GPCRs (metabotropic).

Opioids in ascending pain pathway

↓Substance P & spinal transmission.

Opioids in descending pain pathway

Inhibit projection neurons & excitatory interneurons; activate inhibitory interneurons.

Acupuncture effect on opioids

Increases endogenous opioids; blocked by naloxone.

Gene therapy for pain

HSV vector delivers proenkephalin gene.

Opioids and dopamine reward pathway

Inhibits VTA GABA → ↑DA in NAcc.

Cause of opioid tolerance

Neuroadaptations decrease effect.

Cause of cross-tolerance

Tolerance to one opioid reduces response to others.

Withdrawal timeline

Peaks 36–48 hrs.

Withdrawal symptoms

Pain, nausea, diarrhea, goosebumps, dysphoria.

What is conditioned tolerance?

Learned compensatory responses.

Why overdose risk increases in new environments

Absence of cues reduces tolerance → overdose.

Locus coeruleus activity in withdrawal

Excessive NE firing.

How clonidine reduces withdrawal

α2 agonist ↓NE release.

Methadone advantages

Long-acting, prevents withdrawal, reduces cravings.

Buprenorphine safety feature

Ceiling on respiratory depression.

Purpose of naloxone in Suboxone

Prevents IV misuse.

Naltrexone vs Naloxone

Naloxone = overdose; naltrexone = maintenance.

Reserpine — mechanism and effect

VMAT blocker; depletes monoamines; induces depression.

Dexamethasone — purpose

Tests HPA axis suppression.

PARNATE — mechanism

MAOI; ↑monoamines.

Imipramine — mechanism

TCA; monoamine reuptake block; anticholinergic.

SSRI mechanism

Inhibits 5-HT reuptake.

SNRI mechanism

Blocks NE & 5-HT reuptake.

Ketamine — mechanism

NMDA block; AMPA activation; rapid antidepressant.

Esketamine — mechanism

NMDA block; intranasal.

Tianeptine — mechanism

↑5-HT reuptake; enhances AMPA.

Lithium — mechanism

↑5-HT; ↓catecholamines; neuroprotective.

Valproate — mechanism

↑GABA.

Carbamazepine — mechanism

Na channel stabilizer; GABA_A agonist.

Oxcarbazepine — mechanism

Na channel stabilizer; not GABAergic.

Psilocybin — mechanism

5-HT2A agonist.

DMT — mechanism

5-HT2A agonist

LSD — mechanism

Potent 5-HT2A agonist.

MDMA — mechanism

↑ release of 5-HT, NE, DA.

Ibogaine — mechanism

Modulates NMDA & κ; ↑neurotrophic factors.

Monoamine hypothesis

Low monoamines cause depression.

Evidence supporting monoamine hypothesis

Low 5-HIAA; reserpine evidence; PET ↓5-HT release.

HPA axis in depression

Excess cortisol; abnormal DEX suppression.

REM abnormalities in depression

Short REM latency; ↑REM density; ↓deep sleep.

Forced swim test meaning

Immobility = depressive-like behavior.

Why lithium requires monitoring

Low therapeutic index → toxicity.

Organs monitored with lithium

Kidney & thyroid.

Serotonin produced in gut (%)

95% produced in gut.

Gut bacteria linked to depression

↑Bacteroidetes; ↓Firmicutes.