Exam 3: Psychopharmacology Study Set

PSY 432 GVSU

Morphine, Heroin, Fentanyl, Oxycodone, Methadone, Buprenorphine, etc.

Opioids; Direct agonists binding mainly to mu opioid receptors; mimic endorphins.

Morphine (Pharmacokinetics)

Oral route less effective than the parental route but good for medical use; Parental route leads to stronger affects but increases abuse potential.

***Suboxone (combination of buprenorphine and naloxone)

Partial agonist; when used parentally, naloxone blocks buprenorphine from working; when used orally, naloxone doesn’t work, and buprenorphine does its thing.

***Suboxone in treating heroin addiction.

Has less abuse potential than methadone; the naloxone component prevents buprenorphine from overstimulating the mu-opioid receptors when taken via the parental route of administration.

Salvia

Binds mainly to and activates kappa opioid receptors; mimics dynorphin. Known for its “intense” and “frightening” trips.

Endorphin

Endogenous ligand associated with the mu opioid receptors; known for analgesia, pleasure, and respiratory depression.

Enkephalin

Associated with the delta opioid receptors and pain relief without any of the other side effects.

Dynorphin

Endogenous ligand associated with the kappa opioid receptors; known for analgesia, dysphoria, and stress.

Naloxone (Narcan) and Naltrexone (Revia)

Competitive Opioid Antagonists (used for treatment of drug abuse)

Thorazine (Chlorpromazine) and Haldol (Haloperidol)

Typical Antipsychotics

**Typical Antipsychotics

Mainly competitive antagonists at D-2 Receptors; Treat only the positive symptoms; Extrapyramidal side effects; tardive dyskinesia; histaminergic and anticholinergic side effects. High binding affinity for D2 receptors.

Risperdal (Risperidone) and Zyprexa (Olanzapine)

Atypical Antipsychotics

**Atypical Antipsychotics

Competitive antagonists at D2, D3, D4, and 5HT2A; low binding affinity for D2; high binding affinity for D2 receptors.

Hypofrontality

Decreased activation of the prefrontal cortex contributing to the positive and negative symptoms of schizophrenia. The prefrontal cortex may regulate mesolimbic dopamine activity.

***Why do typical antipsychotics have a higher incidence of extrapyramidal side effects and tardive dyskinesia compared to atypical antipsychotics?

Typical antipsychotics have a high binding affinity for the D2 receptors which have a high density in the nigrostriatal pathway. The nigrostriatal pathway is associated with motor functions. Atypical antipsychotics have a high binding affinity for D3 and D4 receptors and a low binding affinity for D2 receptors. D3 receptors have a high density in the mesolimbic pathway and the D4 receptors have a high density in the mesocortical pathway. These pathways are associated with cognitive and rewarding effects.

Caffeine Pharmacology

The main mechanism of action: Competitive antagonist at A1 and A2a adenosine receptors; Effects on Adenosine System: GABA-A receptor inhibition, Phosphodiesterase inhibition, and intracellular Ca++ release.

Caffeinism

Results from excessive chronic caffeine consumption; anxiety-related symptoms, sensory disturbances.

Adenosine

Inhibitory neuromodulator involved in sleep; regulates cardiac muscles and blood flow.

Examples of Tricyclic Antidepressants

Amitriptyline (Elavil), Imipramine (Tofranil),

Examples of Selective Serotonin Reuptake Inhibitors (SSRIs)

Fluoxetine (Prozac), Escitalopram (Lexapro), Citalopram (Celexa), Fluvoxamine (Luvox), Paroxetine (Paxil), Sertraline (Zoloft)

Examples of Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)

Desvenlafaxine (Pristiq), Duloxetine (Cymbalta), Milnacipran (Ixel), Venlafaxine (Effexor)

Delayed Effects of SSRIs in Alleviating symptoms of depression

Targets long-term biological change. Super sensitivity: serotonin autoreceptors are being activated way too easily. The slightest bit of serotonin can signal an off switch. This leads to a vicious cycle of low levels of serotonin—which increases the density of 5-HT1B autoreceptors. The 2–3-week time point is when enough serotonin build-up begins to over-activate the serotonin autoreceptors leading to downregulation —→ short-circuiting an outlet. Downregulate: shutting off the receptors. No rebound upregulation. Normalizes serotonin levels.

Examples of Indoleamine-like Drugs

LSD, Psilocybin (Magic Mushrooms)

Ecstasy (MDMA)

Indirect agonist that blocks reuptake and enhances the release of neurotransmitters (mainly serotonin). Reverses serotonin reuptake transporter. Mainly increases the transmission of serotonin synapses. Also enhances norepinephrine and dopamine.

Neurotoxic effects of ecstasy

Depletion of serotonin (because of reversal and serotonin being dispersed quickly) leads to sleep disorders, depression, persistent anxiety, selective impairment of memory and attention, and an increase in body temperature. Ecstasy’s increase in serotonin at the synapse is broken down quickly by monoamine oxidase. Serotonin has a high affinity for the presynaptic terminal. Dopamine, being similar to serotonin, gets transported into the presynaptic terminal when there is no serotonin creating hydrogen peroxide and killing neurons. Taking SSRIs blocks the transporter as a competitive antagonist. MAOIs inhibit monoamine oxidase allowing there to be more serotonin (stops the reaction).

Ketamine

Dissociative anesthetic, non-competitive glutamate receptor antagonist that blocks NMDA receptor Ca++ channels.

Dextromethorphan (Robitussin)

Synthetic opioid-like drug. At high doses, dextromethorphan binds with low affinity to the ketamine binding site of the NMDA receptor complex.

Delta-9-Tetrahydrocannibinol (THC)

Direct agonist at cannabinoid receptors that mimics anandamide. High in psychotic effects.

Cannabinol (CBD)

Indirect agonist that prevents metabolism of anandamide. Blocks fatty acid amide hydrolase. Not psychoactive and is converted to delta-9-THC when burned.

Anandamide

Endogenous ligand for brain cannabinoid CB 1 receptors; produces many behavioral effects similar to those of THC.

***THC Pharmacology

Direct agonist at cannabinoid receptors that is high in psychoactive effects. Absorbed faster orally, but higher effects parentally.

**Cerebral Cortex (Cannabinoid Behaviors)

Depolarization-induced suppression of excitation and inhibition; Perception

**Hippocampus (Cannabinoid Behaviors)

Depolarization-induced suppression of excitation; Memory Consolidation

**Basal Ganglia & Cerebellum (Cannabinoid Behaviors)

Depolarization-induced suppression of excitation; Movement & Motor Coordination

** Medulla (Cannabinoid Behaviors)

Depolarization-induced suppression of excitation; nausea & vomiting (relief)e

**Spinal Cord (Cannabinoid Behaviors)

Depolarization-induced suppression of excitation; Pain Relief

**Hypothalamus (Cannabinoid Behaviors)

Depolarization-induced suppression of inhibition; “munchies”

**Amygdala (Cannabinoid Behaviors)

Depolarization-induced suppression of inhibition; emotion (fear/panic)

**Nucleus Accumbens (Cannabinoid Behaviors)

Depolarization-induced suppression of inhibition; Reward/Motivation/Activation

**Neuromodulatory Effects of Anandamide

Activates CB1 receptors triggering an inhibitory G-protein signal, suppressing neurotransmitter release. Leads to depolarization-induced suppression of excitation (neural inhibition) and inhibition (neural excitation).