Learning Objective
Describe the mechanism, examples, and clinical implications of indirect-acting adrenergic agonists (releasers and reuptake inhibitors), and understand the role of MAO in the metabolism of catecholamines.
Releasers
Mechanism: Displace norepinephrine (NE) from the mobile pool in sympathetic nerve terminals. Requires intact sympathetic innervation.
| Drug | Notes / Clinical Use |
|---|---|
| Tyramine | Found in red wine, cheese, oral bioavailability is limited by MAO-A metabolism; Drugs causing MAO-A inhibition → increase the availability of neurotransmitters in the cleft → hypertensive crisis. |
| Amphetamines | Methylphenidate, dextroamphetamine; used in ADHD, narcolepsy; psychostimulant via central release of DA, NE, 5HT of neuronal ending. |
| Pseudoephedrine | Cold medications; mild α1 agonist → nasal decongestant |
Clinical Note: Denervated tissues do not respond to neurotransmitters or neuromodulators.
Reuptake Inhibitors
Mechanism:
Block norepinephrine (and sometimes dopamine/serotonin) reuptake, increasing neurotransmitter levels in the synaptic cleft.
| Drug | Notes |
|---|---|
| Cocaine | Blocks NE reuptake; sympathomimetic and local anesthetic |
| Tricyclic antidepressants (TCA) | Block NE reuptake; used for depression, chronic pain |
| SNRIs | Selective serotonin-norepinephrine reuptake inhibitors |
| Amphetamines | Also inhibits reuptake besides acting as a releaser |
Monoamine Oxidase (MAO)
| MAO Type | Location | Substrate |
|---|---|---|
| MAO-A | Liver (main), gut, other tissues | NE, 5HT, tyramine |
| MAO-B | Brain | Dopamine |
Clinical Implication:
- MAO-A inhibition + dietary tyramine → hypertensive crisis (tyramine “cheese effect”)
- MAO-B inhibition → ↑ dopamine, used in Parkinson’s disease
