AMPT: Catecholamine Depletion Tool

Alpha-methylparatyrosine, universally abbreviated as AMPT, represents one of the most vital pharmacological tools in modern neurobiology and neuropsychiatry. By selectively inhibiting the rate-limiting enzyme in catecholamine biosynthesis, this chemical compound allows researchers and clinicians to temporarily suppress the production of dopamine and norepinephrine, unlocking fundamental insights into human mood, cognition, and neuroendocrine function.

Alpha-Methylparatyrosine (AMPT)

1. Concise Definition

Alpha-methylparatyrosine (AMPT), also designated by the nonproprietary name metirosine, is a competitive inhibitor of the enzyme tyrosine hydroxylase, which catalyzes the conversion of L-tyrosine to L-dihydroxyphenylalanine (L-DOPA). By selectively arresting this initial, rate-limiting stage of catecholamine biosynthesis, AMPT dramatically reduces endogenous pools of dopamine, norepinephrine, and epinephrine across peripheral and central nervous systems.

In experimental neuroscience, AMPT serves as a principal pharmacological challenge agent to study the monoamine hypothesis of affective and psychotic disorders, behavioral reinforcement circuits, and cognitive functions. In medical practice, its primary clinical indication is the preoperative or chronic management of patients presenting with pheochromocytoma, where catecholamine hypersecretion threatens cardiovascular stability.

Pharmacologically classified as an enzyme inhibitor and antihypertensive agent, AMPT operates upstream of post-synaptic receptor machinery, differentiating its physiological effects from direct receptor agonists or antagonists by emptying functional vesicular transmitter reserves rather than occupying target receptor proteins.

2. Etymology & Linguistic Origin

The chemical appellation alpha-methylparatyrosine derives systematically from international organic nomenclature. The prefix "alpha-" (α-) denotes substitution at the primary alpha-carbon adjacent to the carboxylic acid functional moiety of the parent amino acid. The chemical modifier "methyl" refers to the monovalent radical (–CH3) bound to this chiral center, which confers steric hindrance preventing regular enzymatic processing. The positional descriptor "para-" reflects the 1,4-disposition of the hydroxyl group relative to the amino acid side chain on the aromatic benzene ring.

The root term "tyrosine" stems historically from the Greek noun tyros (meaning "cheese"), coined in 1846 by the German chemist Justus von Liebig upon crystallizing the amino acid from casein precipitates. The International Nonproprietary Name (INN) "metirosine" is an elision formed by combining fragments of "methyl," "tyrosine," and the chemical suffix indicating an organic base.

The abbreviation "AMPT" (occasionally rendered as α-MPT) entered the biochemical and neuropharmacological literature during the mid-1960s, gaining ubiquity as research groups sought a succinct moniker for the synthetic compound during competitive inhibition trials of aromatic hydroxylases.

3. Pronunciation & Grammatical Form

Alpha-methylparatyrosine is pronounced phonetically as /æl.fə ˌmɛθ.əl ˌpær.əˈtaɪ.rəˌsin/. Its international nonproprietary counterpart, metirosine, is pronounced /mɛˈtɪr.əˌsin/ or /mɪˈtaɪ.rəˌsin/. The initialism is spoken by pronouncing each letter sequentially: /eɪ ɛm piː tiː/.

Grammatically, the term functions as an uncountable proper noun designating a specific chemical entity. In pharmacological and biochemical contexts, it commonly appears as an attributive noun modifying related experimental procedures, such as "AMPT depletion," "AMPT challenge paradigm," or "AMPT-induced catecholamine blunting." Derived adjectival usage remains uncommon; investigators typically describe physiological models as having undergone "tyrosine hydroxylase inhibition via AMPT" rather than applying morphologically transformed terms.

4. Detailed Conceptual Explanation

To grasp the conceptual scope of alpha-methylparatyrosine, one must analyze the biochemical cascade of catecholamine production. Biosynthesis initiates with the systemic amino acid L-tyrosine, derived from dietary proteins or the hepatic hydroxylation of phenylalanine. Under normal physiological circumstances, tyrosine hydroxylase incorporates molecular oxygen to add a second hydroxyl group onto the aromatic ring of L-tyrosine, generating L-DOPA. This step represents the strict kinetic bottleneck; subsequent conversion of L-DOPA into dopamine via aromatic L-amino acid decarboxylase, and dopamine into norepinephrine via dopamine beta-hydroxylase, occurs at much higher turnover velocities.

AMPT acts as a structural decoy resembling natural L-tyrosine. Because of the alpha-methyl modification, the enzyme binds AMPT with high affinity within its catalytic pocket, yet the enzyme cannot efficiently execute the oxidative transformation. Consequently, AMPT exerts potent, reversible, competitive enzyme inhibition. By occupying catalytic active centers, AMPT suppresses endogenous throughput across the entire downstream pathway.

Within the central nervous system, central catecholamine stores depend continually on de novo synthesis to replenish vesicles depleted through basal neurotransmission and metabolic degradation by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). Following systematic administration of AMPT, brain levels of dopamine and norepinephrine experience an acute decline, often decreasing by 50% to 80% within 24 to 72 hours, depending on dosage protocols.

Importantly, AMPT displays remarkable selectivity: it does not directly interfere with tryptophan hydroxylase, the parallel rate-limiting enzyme in serotonin (5-hydroxytryptamine) synthesis, nor does it inhibit choline acetyltransferase, gamma-aminobutyric acid (GABA) synthesizing enzymes, or glutamate pathways. This pharmacodynamic profile positions AMPT as a pure catecholaminergic sledgehammer, allowing researchers to isolate dopamine and norepinephrine from broader neurochemical systems.

Beyond central applications, the conceptual boundaries of AMPT encompass peripheral autonomic modulation. By blunting peripheral sympathetic output and eliminating excessive adrenal catecholamine release, AMPT reduces systemic vascular resistance, myocardial contractility, and secondary alpha- and beta-adrenergic tone throughout cardiovascular territories.

5. Historical Development

The emergence of AMPT as an experimental and therapeutic agent mirrors the golden era of neurochemical discovery in the mid-twentieth century. In 1964, a research team led by Spector, Sjoerdsma, and Udenfriend at the National Institutes of Health evaluated methylated amino acid analogues in an effort to discover pharmacological compounds capable of controlling severe hypertensive crises. Their classic paper, published in the Journal of Pharmacology and Experimental Therapeutics, demonstrated that alpha-methyl-DL-tyrosine reliably depleted brain and heart catecholamines in rodent models.

Subsequent refinement identified that the levorotatory enantiomer, L-alpha-methyltyrosine, accounted for virtually all biochemical activity, leading to its clinical formulation as metirosine. Throughout the late 1960s, clinicians directed by Jerome Engelman and Albert Sjoerdsma deployed the compound in human subjects diagnosed with pheochromocytoma, a rare catecholamine-secreting neuroendocrine tumor. By demonstrating dramatic decreases in urinary vanillylmandelic acid (VMA) and total catecholamine metabolites, these initial investigations validated AMPT as a functional biochemical blockade.

During the 1970s and 1980s, behavioral pharmacologists adopted AMPT to test the newly formulated catecholamine hypothesis of affective disorders, pioneered by Joseph Schildkraut, William Bunney, and John Davis. Investigators realized that rather than merely observing passive metabolite levels in postmortem tissue, administering AMPT to living humans allowed experimental manipulation of catecholamine states in real time.

In the 1990s and early 2000s, the development of functional neuroimaging technologies—specifically positron emission tomography (PET) using radioligands such as [¹¹C]raclopride and [¹²³I]IBZM—revolutionized AMPT usage. Pioneered by Marc Laruelle, Anissa Abi-Dargham, and Dennis Charney, researchers combined AMPT depletion with radioligand displacement to measure baseline synaptic dopamine concentrations directly in the living human brain, resolving long-standing controversies surrounding catecholaminergic tone in schizophrenia and mood disorders.

6. Theoretical Foundations

The academic study of AMPT intersects with foundational theoretical frameworks in neuropsychiatry and molecular pharmacology. The foremost theoretical construct is the Monoamine Hypothesis of Depression, initially advanced in the 1960s, which posited that depressive states arise from a relative or absolute deficit of monoamines—specifically norepinephrine and dopamine—within critical corticolimbic circuits.

Researchers utilized AMPT challenge paradigms to evaluate this hypothesis empirically. When patients successfully treated with selective norepinephrine reuptake inhibitors (such as desipramine) undergo acute catecholamine depletion via AMPT, a substantial majority experience a transient relapse of depressive symptoms. Conversely, patients treated with selective serotonin reuptake inhibitors (SSRIs) generally remain unaffected by AMPT challenge, experiencing relapses primarily when subjected to acute tryptophan depletion. These empirical demonstrations refined the monoamine framework from a simplistic "single chemical deficiency" model into a nuanced understanding of dissociated, treatment-dependent neurobiological mechanisms.

A second foundational theory relates to the Dopamine Hypothesis of Schizophrenia. Early formulations struggled to distinguish between elevated post-synaptic D2 receptor density and augmented presynaptic dopamine release. AMPT provided the definitive methodology to dissect this dichotomy. By administering AMPT to patients with schizophrenia and scanning them with PET radioligands before and after depletion, researchers demonstrated that patients exhibited heightened displacement of radiotracers, proving that schizophrenia involves an elevated baseline occupancy of D2 receptors by endogenous dopamine—an excess of presynaptic transmitter release.

Furthermore, AMPT informs Reward Deficiency Theory and Reinforcement Learning Frameworks within cognitive neuroscience. Mesolimbic dopamine projections from the ventral tegmental area (VTA) to the nucleus accumbens mediate reward prediction errors and incentive salience. By depleting dopamine with AMPT, cognitive scientists established that dopamine is not strictly required for the sensory experience of pleasure ("liking"), but is essential for motivational drive, effort expenditure, and behavioral reinforcement ("wanting").

7. Key Components, Types & Dimensions

The study and application of alpha-methylparatyrosine span distinct chemical forms, physiological compartments, and dosing dimensions:

• Stereochemical Isomerism: AMPT exists as two enantiomers: L-alpha-methyltyrosine and D-alpha-methyltyrosine. The biological activity resides almost entirely within the L-enantiomer, which matches the stereochemical configuration required for binding to the tyrosine hydroxylase active site. Racemic mixtures (DL-AMPT) require approximately twice the dosage to achieve equivalent enzyme saturation.
• Peripheral vs. Central Action: While AMPT crosses the blood-brain barrier via neutral amino acid transport mechanisms, its effects distribute unevenly across central and peripheral compartments. Peripheral catecholamines in adrenergic nerves and the adrenal medulla deplete rapidly, while central depletion depends on transport saturation and competitive antagonism against circulating plasma amino acids.
• Dosing Protocols (Acute Challenge vs. Chronic Regimen): Experimental psychopharmacology uses acute challenge protocols (typically 4 to 8 grams administered orally over a 24-to-48-hour window) to induce rapid, transient transmitter depletion. Conversely, clinical endocrinological protocols administer sustained daily doses (typically 1 to 4 grams daily in divided portions) titrated to suppress peripheral tumor hypersecretion without producing incapacitating central side effects.
• Biochemical Kinetics: AMPT exhibits predictable pharmacokinetics, with peak plasma concentrations occurring within 2 to 4 hours following oral ingestion. The elimination half-life spans approximately 4 to 7 hours, although central neurochemical depletion persists longer due to the slow recovery of depleted vesicular pools.
• Crystalluria and Renal Solubility: A crucial physicochemical characteristic of AMPT is its low aqueous solubility at physiological urine pH. Because the drug is primarily eliminated unchanged by renal filtration, it crystallizes readily in renal tubules when urine volumes drop, introducing a clinical dimension that demands strict fluid management.

8. Examples & Illustrative Cases

The operational dynamics of AMPT become clear through real-world scenarios across research and clinical oncology.

Case Illustration 1: Investigating Relapse Vulnerability in Major Depression
A 45-year-old patient diagnosed with recurrent major depressive disorder has achieved sustained clinical remission using reboxetine, a selective noradrenergic reuptake inhibitor. Under an institutional review board-approved protocol, the patient undergoes a double-blind, randomized AMPT challenge. Over 28 hours, the patient receives 4.5 grams of AMPT divided into multiple oral capsules. Urinary catecholamine metabolite assays confirm a 75% reduction in 3-methoxy-4-hydroxyphenylglycol (MHPG). Within 36 hours from baseline, the patient develops a transient, severe return of depressive symptoms, including apathy, psychomotor slowing, and low mood. Following clearance of the drug and restoration of endogenous catecholamines over the subsequent 48 hours, the depressive symptoms resolve completely. This case demonstrates that remission supported by noradrenergic mechanisms relies on continuous presynaptic transmitter synthesis.

Case Illustration 2: Preoperative Optimization of Pheochromocytoma
A 32-year-old individual presents with paroxysmal hypertensive crises, profuse diaphoresis, and severe cephalalgia. Cross-sectional imaging reveals a 4.5-centimeter mass within the right adrenal gland, and plasma free metanephrines are elevated more than ten times above reference limits, confirming pheochromocytoma. Although alpha-adrenergic blockade using phenoxybenzamine is initiated, the patient continues to experience blood pressure volatility. The endocrine surgery team introduces oral metirosine at 250 mg four times daily, gradually titrating to 2 grams daily alongside vigorous oral hydration. The synthesis inhibitor rapidly blunts intra-tumoral catecholamine stores. During laparoscopic tumor resection two weeks later, intraoperative manipulation produces minimal hemodynamic swings, avoiding malignant hypertensive peaks and postoperative cardiovascular collapse.

9. Measurement & Assessment

Because AMPT is a probe rather than an endophenotype, assessment protocols focus on quantifying its pharmacological absorption, evaluating downstream catecholaminergic depletion, and monitoring adverse reactions.

The efficacy of AMPT administration is assessed biochemically via high-performance liquid chromatography (HPLC) coupled with electrochemical detection or tandem mass spectrometry (LC-MS/MS). These analytical platforms measure parent catecholamines and their major metabolic breakdown products:

• Homovanillic acid (HVA): The primary peripheral and central metabolite of dopamine, reflecting central dopaminergic turnover.
• 3-Methoxy-4-hydroxyphenylglycol (MHPG): The primary central metabolite of norepinephrine capable of traversing the blood-brain barrier into plasma and urine.
• Vanillylmandelic acid (VMA): The end-stage peripheral urine metabolite reflecting total systemic noradrenergic and adrenergic output.

Neuroimaging assessment employs PET or single-photon emission computed tomography (SPECT). Investigators use dopamine D2/D3 receptor antagonists such as [¹¹C]raclopride, [¹⁸F]fallypride, or [¹²³I]IBZM. When AMPT empties endogenous dopamine from the synaptic cleft, these radioligands bind in greater numbers to unoccupied receptors, producing an elevated binding potential ($BP_ ext{ND}$). The difference between baseline $BP_ ext{ND}$ and post-AMPT $BP_ ext{ND}$ serves as a direct quantitative metric of baseline synaptic dopamine concentration.

Clinical safety monitoring relies on routine urinalysis. Due to the high risk of drug crystalluria, urine specimens are spun and examined under phase-contrast microscopy to detect characteristic needle-shaped metirosine crystals. Daily fluid output is maintained above 2,000 to 3,000 milliliters, and urine specific gravity is systematically monitored alongside serum creatinine levels.

10. Applications & Practical Significance

The applications of AMPT span diagnostic exploration, pharmacological modeling, and acute medical management:

• Endocrine Oncology: Metirosine is clinically approved by major regulatory authorities (including the US FDA) for managing patients with pheochromocytoma. It stabilizes patients preoperatively when single-agent alpha- and beta-receptor blockade proves inadequate, and provides chronic palliation for inoperable, malignant, or metastatic chromaffin tissue tumors.
• Dissecting Antidepressant Mechanics: AMPT challenge remains an indispensable paradigm to categorize psychiatric therapies. It reveals whether novel antidepressant, anxiolytic, or stimulant agents exert therapeutic efficacy through direct catecholaminergic mechanisms versus downstream neuroplastic, serotonergic, or glutamatergic pathways.
• Addiction and Substance Abuse Studies: Addictive substances—including psychostimulants (cocaine, methamphetamine), alcohol, and nicotine—depend on elevated mesolimbic dopamine signaling to consolidate conditioned reinforcement. Pretreatment with AMPT blocks drug-induced dopamine spikes, allowing cognitive neuroscientists to assess subjective drug "high," craving intensity, and self-administration behaviors in both preclinical models and human clinical research.
• Modeling Parkinsonian Features: Because severe catecholamine depletion mimics the degenerative loss of substantia nigra pars compacta neurons, experimental AMPT exposure produces temporary, dose-dependent Parkinsonian signs, including muscular rigidity, resting tremor, bradykinesia, and postural instability. This reversible model enables researchers to study basal ganglia dynamics without causing permanent neurotoxic damage.

11. Research & Empirical Evidence

Dozens of pivotal studies spanning five decades underscore the empirical utility of AMPT in brain mapping, psychiatric phenomenology, and cellular biochemistry.

In a seminal paper, Charney et al. (1996) investigated unipolar depressed patients in sustained remission on varied pharmacotherapies. Patients maintained on noradrenergic agents (such as desipramine, nomifensine, or reboxetine) exhibited rapid depressive relapses following double-blind AMPT depletion. In striking contrast, patients maintained on selective serotonin reuptake inhibitors (fluoxetine, sertraline) rarely relapsed under identical AMPT regimens. These findings provided empirical validation that disparate molecular interventions achieve remission through distinct monoaminergic signaling cascades.

In schizophrenia research, Laruelle and colleagues (1996, 1999) used AMPT challenge alongside SPECT imaging to resolve the controversy surrounding presynaptic dopamine function. By demonstrating that patients diagnosed with schizophrenia exhibited significantly greater increases in radiotracer binding potential post-AMPT compared to neurotypical controls, they established that schizophrenia pathophysiology involves heightened baseline occupancy of striatal D2 receptors, confirming elevated presynaptic dopamine release.

Furthermore, behavioral studies exploring human anhedonia and motivation by Hasler et al. (2008) and Treadway et al. demonstrated that AMPT depletion selectively diminishes an individual's willingness to expend physical or cognitive effort for prospective monetary rewards. Even when self-reported subjective pleasure upon receiving a reward remains largely unchanged, the reduction of central dopamine synthesis degrades willingness to engage in effortful goal-directed behavior, helping disentangle motivational anhedonia from consummatory anhedonia.

12. Cultural & Cross-Cultural Considerations

While the biochemical actions of AMPT are conserved across human biology, cross-cultural and regional variations emerge in clinical implementation, research ethics, and regulatory frameworks.

Globally, access to metirosine remains uneven. In high-income countries with specialized tertiary endocrine centers, metirosine is stockpiled for complex pheochromocytoma surgeries. In developing or resource-constrained healthcare systems, high manufacturing costs and limited distribution networks make the drug largely unavailable. Clinicians in these regions rely almost entirely on non-selective alpha-antagonists (such as phenoxybenzamine) and calcium channel blockers for perioperative tumor management.

Ethical review frameworks for non-therapeutic, experimental AMPT challenges in human volunteers also vary internationally. In North American and Western European academic medical centers, institutional review boards permit psychiatric challenge studies only under stringent informed consent, inpatient monitoring, and emergency rescue protocols. Some international regulatory authorities, by contrast, discourage pharmacological challenges that deliberately provoke acute depressive relapses or transient psychosis, prioritizing lower-risk observational or neuroimaging paradigms.

Furthermore, physiological variables tied to regional diets and genetic polymorphisms warrant attention. Diets containing variable quantities of precursor neutral amino acids (such as high-protein diets rich in natural L-tyrosine and L-phenylalanine) can competitively modulate the transport of AMPT across the blood-brain barrier via the Large Neutral Amino Acid Transporter 1 (LAT1), introducing pharmacokinetic variance across diverse global research cohorts.

13. Criticisms, Debates & Limitations

Despite its historic achievements, the use of AMPT faces important methodological, safety, and conceptual criticisms.

First, AMPT lacks neurochemical specificity between catecholamines. Because tyrosine hydroxylase is the shared rate-limiting step for both dopamine and norepinephrine synthesis, administering AMPT depletes both neurotransmitters simultaneously. When an experimental subject develops apathy, sedation, executive deficits, or a depressive relapse during challenge, researchers cannot definitively attribute the outcome to dopamine reduction alone, norepinephrine reduction alone, or synergistic interactions between the two systems.

Second, safety concerns constrain the practical utility of the drug. The high propensity for metirosine crystalluria requires aggressive oral and intravenous hydration (often exceeding 3 to 4 liters per day) alongside regular urinary monitoring. The risk of acute crystal nephropathy, combined with pronounced side effects—such as profound daytime somnolence, akathisia, anxiety, dysphoria, diarrhea, and extrapyramidal symptoms—restricts the safe application of high-dose AMPT paradigms to closely monitored inpatient or laboratory settings.

Finally, adaptive neurochemical counter-regulations complicate longitudinal studies. Prolonged or repeated administration of AMPT initiates homeostatic adaptations, including the upregulation of post-synaptic D2 and beta-adrenergic receptors and altered firing rates in midbrain monoamine neurons. Consequently, sustained treatment changes baseline neuroreceptor architecture, confounding experiments designed to isolate normal, unperturbed biological function.

14. Related Terms & Distinctions

To avoid conceptual and pharmacological confusion, AMPT should be differentiated from structurally or functionally related entities:

• Reserpine: While both substances deplete monoamines, reserpine acts by irreversibly inhibiting the Vesicular Monoamine Transporter (VMAT-1 and VMAT-2), preventing intravesicular storage and precipitating monoamine degradation. AMPT, by contrast, inhibits the synthetic enzyme tyrosine hydroxylase, leaving VMAT function intact. Reserpine also depletes serotonin, whereas AMPT selectively preserves serotonergic reserves.
• Carbidopa: Carbidopa is an enzyme inhibitor targeting aromatic L-amino acid decarboxylase (DOPA decarboxylase). It operates downstream of tyrosine hydroxylase and, crucially, does not cross the blood-brain barrier at therapeutic doses, restricting its activity to the periphery. AMPT readily penetrates the central nervous system and acts on the upstream, rate-limiting enzyme.
• Para-Chlorophenylalanine (PCPA): PCPA is a selective synthetic inhibitor of tryptophan hydroxylase, the rate-limiting enzyme in serotonin biosynthesis. While AMPT depletes catecholamines, PCPA depletes serotonin, making the two compounds complementary pharmacological tools for dissecting monoaminergic pathways.
• 6-Hydroxydopamine (6-OHDA): 6-OHDA is a neurotoxin that destroys catecholaminergic nerve terminals via oxidative stress and mitochondrial damage, causing permanent structural lesions. In contrast, AMPT produces temporary, reversible biochemical inhibition without structural neurotoxicity.

15. Summary / Key Takeaways

Alpha-methylparatyrosine (AMPT; metirosine) is the classic competitive inhibitor of tyrosine hydroxylase, the rate-limiting enzyme responsible for catecholamine synthesis. By shutting down the de novo synthesis of dopamine, norepinephrine, and epinephrine, AMPT reliably diminishes central and peripheral catecholaminergic tone.

Clinically, metirosine remains a specialized, life-saving agent for the preoperative and chronic hemodynamic stabilization of patients harboring pheochromocytoma. In clinical and translational neuroscience, the compound serves as an invaluable probe that catalyzed the validation of the monoamine hypothesis of mood disorders, verified elevated presynaptic dopamine synthesis in schizophrenia, and enabled direct quantification of baseline synaptic transmitter levels via PET neuroimaging.

Although limited by its non-selective depletion of both dopamine and norepinephrine, as well as risks of crystalluria and extrapyramidal side effects, AMPT remains an irreplaceable pillar of clinical psychopharmacology and endocrine research.

References

• Charney, D. S., Delgado, P. L., & Price, L. H. (1996). The receptor sensitivity hypothesis of antidepressant action: A review of pharmacological challenge studies. Journal of Clinical Psychiatry, 57(Suppl 4), 5–14.
• Engelman, K., Horwitz, D., Jequier, E., & Sjoerdsma, A. (1968). Biochemical and pharmacologic effects of alpha-methyltyrosine in man. The Journal of Clinical Investigation, 47(3), 577–594. https://doi.org/10.1172/JCI105754
• Hasler, G., Fromm, S., Carlson, P. J., Luckenbaugh, D. A., Waldeck, T., Geraci, M., Roiser, J. P., Neumeister, A., Shen, J., & Drevets, W. C. (2008). Neural response to reward and punishment in the unmedicated remission state of major depressive disorder: An AMPT challenge study. The American Journal of Psychiatry, 165(4), 521–531. https://doi.org/10.1176/appi.ajp.2007.07060867
• Laruelle, M., Abi-Dargham, A., van Dyck, C. H., Gil, R., D'Souza, C. D., Erdos, J., McCance, E., Rosenblatt, W., Fingado, C., Zoghbi, S. S., Baldwin, R. M., Seibyl, J. P., Krystal, J. H., Charney, D. S., & Innis, R. B. (1996). Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proceedings of the National Academy of Sciences, 93(17), 9235–9240. https://doi.org/10.1073/pnas.93.17.9235
• Spector, S., Sjoerdsma, A., & Udenfriend, S. (1965). Blockade of endogenous norepinephrine synthesis by alpha-methyl-tyrosine, an inhibitor of tyrosine hydroxylase. Journal of Pharmacology and Experimental Therapeutics, 147(1), 86–95. https://jpet.aspetjournals.org/content/147/1/86