Tetrabenazine

Key takeaways

Tetrabenazine belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Tetrabenazine to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Tetrabenazine from memory before moving on to harder problems.

Reference excerpt

Tetrabenazine is a drug for the symptomatic treatment of hyperkinetic movement disorders. It is sold under the brand names Nitoman and Xenazine among others. On August 15, 2008, the US Food and Drug Administration (FDA) approved the use of tetrabenazine to treat chorea associated with Huntington's disease. Although other drugs had been used "off-label", tetrabenazine was the first approved treatment for Huntington's disease in the United States. The compound has been known since the 1950s.

Medical uses Tetrabenazine is used as a treatment, but not as a cure, for hyperkinetic disorders such as:

Huntington's disease – specifically, the chorea associated with it Tourette syndrome and other tic disorders Tardive dyskinesia, a serious and sometimes irreversible side effect of long-term use of many antipsychotics, mainly typical antipsychotics Hemiballismus, spontaneous flinging limb movements on one side of the body due to damage to the subthalamic nucleus on the other side Tetrabenazine has been used as an antipsychotic in the treatment of schizophrenia, both in the past and in modern times.

Adverse effects The most common adverse effects, which have occurred in at least 10% of subjects in studies and at least 5% greater than in subjects who received placebo, have been: sedation or somnolence, fatigue, insomnia, depression, suicidal thoughts, akathisia, anxiety, and nausea. It has also been reported to produce apathy.

Black box warning There is a boxed warning associated with the use of tetrabenazine:

Increases the risk of depression and suicidal thoughts and behavior in patients with Huntington's disease Balance risks of depression and suicidality with the clinical need for control of chorea when considering the use of tetrabenazine Monitor patients for emergence or worsening of depression, suicidality or unusual changes in behavior Inform patients, caregivers and families of the risk of depression and suicidality and instruct to report behaviours of concern promptly to the treating physician Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation Tetrabenazine is contraindicated in patients who are actively suicidal and in patients with untreated or inadequately treated depression

Pharmacology

The precise mechanism of action of tetrabenazine is unknown. Its anti-chorea effect is believed to be due to a reversible depletion of monoamines such as dopamine, serotonin, norepinephrine, and histamine from nerve terminals. Tetrabenazine reversibly inhibits vesicular monoamine transporter 2 (VMAT2), resulting in decreased uptake of monoamines into synaptic vesicles, as well as depletion of monoamine storage.

Research

Animal model of motivational dysfunction

Tetrabenazine is used in the only animal model of motivational dysfunction. The drug results in selective depletion of dopamine at low doses of 0.25 to 1.0 mg/kg and induces a low-effort bias in effort-based decision-making tasks at these doses. It has been found to reduce striatal or nucleus accumbens dopamine levels by 57 to 75% at a dose of 0.75–1.0 mg/kg in rats. In contrast, levels of serotonin and norepinephrine are only reduced by up to 15 to 30% at this dosage. A 10-fold higher dosage of 10 mg/kg is needed to decrease serotonin levels as much as the reduction in dopamine levels at 1 mg/kg. The low-effort bias of systemic administration of tetrabenazine also occurs when it is injected directly into the nucleus accumbens but not the overlying medial neostriatum (i.e., dorsal striatum). Dopamine D1 receptor antagonists like ecopipam and dopamine D2 receptor antagonists like haloperidol have similar amotivational effects as tetrabenazine in animals. A number of pro-motivational drugs have been found to reverse the amotivational effects of tetrabenazine. These include the dopamine releasing agent lisdexamfetamine, the dopamine reuptake inhibitors methylphenidate, bupropion, modafinil, vanoxerine, PRX-14040, and MRZ-9547, and the MAO-B inhibitor and catecholaminergic activity enhancer selegiline. Selegiline shows a complicated U-shaped dose–response curve in its efficacy in the model. In contrast to the preceding agents, many antidepressants, including selective serotonin reuptake inhibitors (SSRIs) like fluoxetine and citalopram, the norepinephrine reuptake inhibitors (NRIs) desipramine and atomoxetine, the selective MAO-A inhibitor moclobemide, and the non-selective monoamine oxidase inhibitor pargyline, are ineffective in reversing tetrabenazine-induced amotivational symptoms. SSRIs and NRIs actually induced further motivational impairments at high doses.

Dyskinetic cerebral palsy A retrospective longitudinal study in a cohort of 23 children with dyskinetic cerebral palsy was conducted where they were treated with tetrabenazine. Results showed significant improvement in movement disorders over time. The study supports tetrabenzine's potential for DCP treatment and shows that the MD-CRS 4-18 scale is a tool for tracking progress in future clinical trials.

Illustrations

Worked examples

Example 1 — a first encounter with Tetrabenazine

Start with the simplest possible case. Write down what Tetrabenazine claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Tetrabenazine before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Tetrabenazine ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Tetrabenazine

In research: Tetrabenazine appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Tetrabenazine in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Tetrabenazine is common in secondary-school and first-year university syllabi. It links to neighbouring topics Antidyskinetic agents, Anxiogenics, Cyclic ketones, so understanding it makes those chapters shorter.
In everyday life: Look for Tetrabenazine outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study Tetrabenazine in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Tetrabenazine means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Tetrabenazine out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Tetrabenazine in simple terms?

Tetrabenazine is a drug for the symptomatic treatment of hyperkinetic movement disorders. It is sold under the brand names Nitoman and Xenazine among others.

Why does Tetrabenazine matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Tetrabenazine?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Tetrabenazine.