Biogenic Amines Flashcards

Vocabulary flashcards summarizing key terms, structures, receptors, enzymes, pathways and therapeutics related to biogenic amine neurotransmission.

Biogenic amines

Small-molecule neurotransmitters that include catecholamines, serotonin, histamine and acetylcholine, modulating cognition, mood, arousal and motor function.

Catecholamines

The subgroup of biogenic amines composed of dopamine, norepinephrine and epinephrine, all derived from tyrosine.

Serotonin (5-HT)

Tryptophan-derived monoamine that regulates mood, anxiety, sleep, appetite and cognition; synthesized in raphe nuclei.

Histamine (CNS)

Biogenic amine produced by tuberomammillary nucleus neurons that promotes wakefulness and arousal.

Acetylcholine (ACh)

Neurotransmitter essential for learning, memory, attention, autonomic function and neuromuscular transmission.

Autoreceptor

Presynaptic receptor for the neuron’s own transmitter that provides negative feedback to inhibit further release.

Heteroreceptor

Presynaptic receptor activated by a different neurotransmitter, modulating release positively or negatively.

Nigrostriatal pathway

Dopaminergic tract (A9) from substantia nigra to striatum, critical for motor control and habit formation.

Mesolimbic pathway

Dopamine projection (A10) from VTA to nucleus accumbens and limbic areas that mediates reward and motivation.

Mesocortical pathway

Dopamine fibers (A10) from VTA to prefrontal cortex involved in executive function and working memory.

Tuberoinfundibular pathway

Hypothalamic dopamine projection that suppresses prolactin release from the anterior pituitary.

Tonic dopamine firing

Single-spike activity that maintains basal extracellular dopamine supporting ongoing motor, cognitive and motivational functions.

Phasic dopamine firing

Burst activity releasing larger dopamine amounts that encode reward prediction error signals.

Parkinson’s disease

Neurodegenerative loss of nigrostriatal dopamine producing hypokinesia, rigidity and tremor; treated with L-dopa and DA agonists.

Tardive dyskinesia

Involuntary movements arising from chronic dopamine receptor blockade, typically by antipsychotics.

Schizophrenia (dopamine hypothesis)

Positive symptoms linked to excess dopamine in associative striatum; negative/cognitive symptoms linked to diminished PFC dopamine.

COMT Val158Met polymorphism

Genetic variant where Met158 lowers COMT activity, raising PFC dopamine and affecting cognition and stress sensitivity.

Inverted U-shaped dopamine curve

Concept that optimal (intermediate) dopamine levels maximize cognitive performance, whereas too little or too much impairs it.

Tyrosine hydroxylase

Rate-limiting enzyme converting tyrosine to L-dopa in catecholamine synthesis.

Aromatic amino acid decarboxylase (AADC)

Enzyme that decarboxylates L-dopa to dopamine and 5-HTP to serotonin.

Dopamine-β-hydroxylase (DBH)

Vesicular enzyme transforming dopamine into norepinephrine.

Phenylethanolamine-N-methyltransferase (PNMT)

Cytoplasmic enzyme that methylates norepinephrine to epinephrine.

Vesicular monoamine transporter 2 (VMAT-2)

Protein that loads monoamines into synaptic vesicles; disrupted by amphetamines.

Dopamine transporter (DAT)

Plasma-membrane carrier that recaptures dopamine; blocked by cocaine and amphetamines.

Norepinephrine transporter (NET)

Reuptake carrier for norepinephrine (and epinephrine); inhibited by TCAs, SNRIs, NRIs.

Monoamine oxidase A (MAO-A)

Mitochondrial enzyme preferring dopamine and norepinephrine catabolism.

Monoamine oxidase B (MAO-B)

Isoform degrading serotonin and phenylethylamine; inhibited by selegiline in Parkinson’s therapy.

Catechol-O-methyltransferase (COMT)

Cytosolic and membrane enzyme that O-methylates catecholamines; inhibited by tolcapone and entacapone.

Homovanillic acid (HVA)

Major dopamine metabolite measured in CSF and plasma.

MHPG (3-methoxy-4-hydroxyphenylglycol)

Principal central metabolite of norepinephrine.

Vanillylmandelic acid (VMA)

Peripheral metabolite of norepinephrine and epinephrine used in pheochromocytoma diagnosis.

Levodopa (L-dopa)

Dopamine precursor that crosses the BBB to replenish striatal dopamine in Parkinson’s disease.

Carbidopa

Peripheral AADC inhibitor co-given with L-dopa to reduce systemic side effects.

Typical antipsychotics

First-generation drugs (e.g., haloperidol) that strongly block D2 receptors but cause extrapyramidal symptoms.

Atypical antipsychotics

Second-generation agents (e.g., clozapine, risperidone) blocking D2 and 5-HT2A with lower EPS but metabolic risks.

D1-like receptors

D1 and D5 dopamine receptors coupled to Gs that stimulate adenylate cyclase and are predominantly postsynaptic.

D2-like receptors

D2, D3, D4 receptors coupled to Gi that inhibit adenylate cyclase; D2 also functions as an autoreceptor.

Locus Coeruleus (LC)

Noradrenergic nucleus in the pons providing widespread NE projections influencing arousal and attention.

Tonic NE firing

Baseline LC activity associated with behavioral flexibility and sustained attention.

Phasic NE firing

Burst LC activity evoked by salient stimuli, enhancing focused attention.

α1-Adrenergic receptor

Postsynaptic Gq-coupled receptor mediating vasoconstriction; targeted by phenylephrine (agonist) and prazosin (antagonist).

α2-Adrenergic receptor

Pre-/postsynaptic Gi-coupled receptor that inhibits NE release and improves PFC function; activated by clonidine and guanfacine.

β-Adrenergic receptors

Gs-coupled subtypes β1 (cardiac), β2 (bronchodilation), β3 (lipolysis); antagonized by propranolol, metoprolol.

Epinephrine (adrenaline)

Final catecholamine of sympathetic system; mediates stress, cardiovascular and metabolic responses.

Serotonin transporter (SERT)

High-affinity reuptake protein for 5-HT; primary target of SSRIs.

Raphe nuclei

Midline brainstem clusters (dorsal & median) that house serotonergic cell bodies projecting widely.

5-HT1A receptor

Gi-coupled autoreceptor/postsynaptic receptor modulating mood; agonist buspirone is an anxiolytic.

Triptans

5-HT1B/1D receptor agonists (e.g., sumatriptan) that relieve migraine by inhibiting cranial vasodilation and neuropeptide release.

5-HT2A receptor

Gq-coupled receptor influencing perception and cognition; agonized by LSD, antagonized by atypical antipsychotics.

5-HT3 receptor

Ligand-gated ion channel mediating fast excitation; antagonists like ondansetron treat chemotherapy-induced nausea.

5-HT4 receptor

Gs-coupled receptor enhancing GI motility; agonist cisapride once used for gastroparesis.

Acetylcholinesterase inhibitor (donepezil)

Drug that blocks ACh breakdown to improve cognition in Alzheimer’s disease.

Basal forebrain cholinergic complex

Medial septum, diagonal band and nucleus basalis neurons projecting to cortex and hippocampus for learning and memory.

Muscarinic M1 receptor

Gq-coupled cholinergic receptor in cortex/hippocampus important for cognitive processing.

Muscarinic M4 receptor

Gi-coupled receptor in striatum modulating motor circuits; M1/M4 agonist xanomeline shows antipsychotic potential.

Nicotinic α4β2 receptor

Most common CNS nicotinic receptor; partial agonist varenicline aids smoking cessation.

Nicotinic α7 receptor

Homomeric nicotinic channel linked to cognition; target for Alzheimer’s and schizophrenia drug development.

Galantamine

AChE inhibitor and positive allosteric modulator of nicotinic receptors used in Alzheimer’s therapy.

Benztropine

Central muscarinic antagonist employed to counteract Parkinsonian tremor and EPS.

Botulinum toxin

Protease that blocks ACh release at neuromuscular junction causing flaccid paralysis.

Sarin gas

Irreversible organophosphate AChE inhibitor leading to cholinergic crisis.

H3 receptor

Presynaptic histamine autoreceptor (Gi) that inhibits histamine release; inverse agonist pitolisant treats narcolepsy.

H4 receptor

Histamine receptor expressed on immune cells; investigated for allergy, asthma and pruritus therapy.

Trace amines

Endogenous, low-level amines (e.g., phenylethylamine, tyramine) easily crossing membranes and rapidly degraded by MAO.

TAAR1 (Trace amine-associated receptor 1)

GPCR highly expressed in VTA and raphe; activation dampens dopamine and serotonin neuron firing.

TAAR1 agonists

Experimental compounds in trials for schizophrenia and addiction, showing no abuse liability.

VMAT-disrupting amphetamines

Psychostimulants that collapse vesicular pH gradient, increasing cytosolic and extracellular dopamine.

Pramipexole

D2/D3 dopamine agonist used to treat Parkinson’s disease and restless legs syndrome.

Risperidone

Atypical antipsychotic with notable D2 and 5-HT2A antagonism; prone to causing hyperprolactinemia.

Clozapine

Treatment-resistant antipsychotic effective on positive and negative symptoms but carries agranulocytosis risk.

Prazosin

α1-adrenergic antagonist used for hypertension, PTSD nightmares, and benign prostatic hyperplasia.

Clonidine

α2-adrenergic agonist that lowers sympathetic tone, treats hypertension, ADHD, and opioid withdrawal.

Propranolol

Non-selective β-blocker for hypertension, ischemic heart disease and performance/social anxiety.

MAOI dietary restriction

Need to avoid tyramine-rich foods to prevent hypertensive crisis during non-selective MAO inhibition.

Ondansetron

Selective 5-HT3 antagonist used to prevent chemotherapy-induced nausea and vomiting.

Lurasidone

Antipsychotic with 5-HT7 antagonism benefiting bipolar depression and schizophrenia cognition.

D1–D2 receptor heteromer

GPCR complex with unique signaling properties, representing a future pharmacologic target.