Lecture Notes on Amphetamines

Flashcards covering key vocabulary and concepts from a lecture on amphetamines, their history, synthesis, effects, and analysis.

Amphetamine

A class of phenethylamine compounds with sympathomimetic activity, mimicking neurotransmitters that stimulate the sympathetic nervous system.

Amphetamine Mechanisms of Action

Releasing endogenous neurotransmitters and inhibiting reuptake of norepinephrine, dopamine, and serotonin.

Historical Context of Amphetamines

First synthesized in 1877; introduced clinically in the 1930s for narcolepsy and depression, later recognized for abuse potential due to fatigue relief, euphoria, and enhanced mood/performance.

Wartime Use of Amphetamines

Widespread use among soldiers, factory workers, and POWs during WWII, particularly in Japan, leading to surplus and abuse post-war.

Illicit Production Hotspots

Pacific Coast, Hawaii, Japan, and Korea, with methamphetamine labs comprising >50% of DEA seizures in the late 1970s–early 1980s.

P2P Reductive Amination

Early synthesis method (1970s–1980s) involving phenyl-2-propanone (P2P), methylamine, aluminum foil, mercuric chloride, and alcohol.

Ephedrine-Based Synthesis

Reduction of ephedrine (EPH) and pseudoephedrine (PE) using hydroiodic acid (HI) and red phosphorus, or thionyl chloride (1990s).

Designer Drugs Intent

Illicit chemists tweak molecular structures of amphetamines/methamphetamines to evade legal scheduling, create legal highs, and maintain similar CNS stimulant or hallucinogenic effects

MDMA

Methamphetamine analog, also known as Ecstasy, XTC, or Adam.

MDA

Amphetamine analog, N-demethylated MDMA metabolite.

Khat

Catha edulis (East Africa, Arabian Peninsula) chewed for cultural/religious tradition; contains active compounds like cathinone, cathine, and norephedrine.

Synthetic Cathinones

Designer drugs modeled after cathinone, often sold as bath salts, plant food, or stain removers to evade legal regulation.

Common routes of use for synthetic cathinones

Oral ingestion (“bombing” wrapped in paper), snorting, smoking, intravenous (IV) or intramuscular (IM) injection

Methcathinone

Synthesized in 1928

Mephedrone

Synthesized in 1929 and known as 4-MMC

Bupropion

Therapeutic cathinone derivative used as antidepressant & smoking cessation aid

Methamphetamine and amphetamine act by

Displacing dopamine (DA) from synaptic vesicles and inhibiting reuptake transporters for DA, norepinephrine (NE), and serotonin (5-HT), increasing extracellular concentrations of these neurotransmitters

Central Nervous System (CNS) Stimulation Effects

Euphoria, increased alertness and confidence, reduced fatigue, and enhanced motor activity.

MDMA and MDA combine

Stimulant and hallucinogenic properties such as empathy, euphoria, introspection, with CNS stimulation risks like hyperthermia, convulsions, rhabdomyolysis

Short-term Adverse Effects of Amphetamines

Tachycardia, hypertension, insomnia, hyperthermia, nausea, paranoia, hallucinations.

Long-term/High-Dose Adverse Effects of Amphetamines

Psychosis, seizures, cardiovascular complications, neurotoxicity.

Methamphetamine: The Drug of Choice

Popular due to ease of synthesis, potent CNS effects, and versatile routes: oral, IV, smoking, insufflation

Crystalline Methamphetamine

Known as “Ice”, it's a highly pure, smokable form

Powder Methamphetamine

Known as “Speed,” “Crank”, may be adulterated with sugars, caffeine, etc.

MDMA (Ecstasy) and MDA:

Abused for psychoactive & hallucinogenic effects, with synthetic routes widely shared online; most labs produce racemic mixtures

MDMA causes

5-HT neurotoxicity causing selective damage to serotonergic terminals, resulting in decreased serotonin (5-HT) and tryptophan hydroxylase (TPH) activity.

Effects of MDMA Neurotoxicity

Memory loss, mood instability and Parkinson-like symptoms in chronic users.

Methamphetamine Excretion

45% excreted unchanged in urine; 7% metabolized to Amphetamine via N-demethylation. Elimination: Acidic urine decreases half-life (7–8 h); alkaline urine increases half-life (18–34 h).

Sympathomimetic Amines (EPH, PE, PPA) excretion

Mostly excreted unchanged and highly pH-dependent.

Immunoassay Techniques

Rapid, cost-effective screening method for amphetamines in matrices like urine, blood, and postmortem fluids.

Gas Chromatography (GC) for Amphetamine Analysis

Early elution for Amphetamine, meth, PPA, MDA, MDMA, mephedrone; derivatization improves analysis by reducing peak tailing, increasing retention and separation.

Liquid Chromatography (LC)

Widely used, no derivatization needed; compatible with protein precipitation and offers greater specificity for complex samples.

Toxic CNS Effects of Amphetamines

Anxiety, agitation, hallucinations, seizures, paranoia, amphetamine psychosis.

Cardiovascular Effects of Amphetamines

Hypertension, tachycardia, arrhythmias, myocardial ischemia, stroke due to vasospasm or hypertension.

Close-Up Forever Summer Concert Tragedy (2016)

In May 2016, five individuals aged 18 to 36 died after attending the Close-Up Forever Summer concert in Pasay City. Autopsies revealed that the victims had ingested a potent mix of party drugs, including ecstasy and methamphetamine derivatives. The substances caused massive organ damage, leading to heart failure and brain swelling.

Ashley Abad's Overdose (2019)

During the Sinulog Festival in Cebu, 19- year-old Ashley Abad collapsed at a pre- festival concert and later died. An autopsy confirmed that she succumbed to an ecstasy overdose.