benserazide

Action and Spectrum

Actions and Spectrum: 

• The mechanism of action of benserazide involves inhibiting the enzyme aromatic L-amino acid decarboxylase (also known as DOPA decarboxylase) in the peripheral tissues outside the central nervous system (CNS).  
• This enzyme converts levodopa to dopamine in these peripheral tissues, significantly reducing levodopa’s effectiveness when treating Parkinson’s disease. 
• By inhibiting DOPA decarboxylase, benserazide ensures that a larger proportion of levodopa reaches the brain, which can be converted to dopamine and alleviate the symptoms of Parkinson’s disease.  
• Dopamine is deficient in the brains of Parkinson’s patients, and levodopa, a precursor to dopamine, can help replenish dopamine levels. 
• The spectrum of activity of benserazide is limited to its peripheral actions, specifically in the body’s peripheral tissues. It does not directly affect the central nervous system, so its primary role is to enhance the delivery and effectiveness of levodopa in the brain. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Cardiac arrhythmias 

Nausea 

Abnormal involuntary movements 

Insomnia 

headache 

Flushing 

Hand tremor 

Stomach upset 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: benserazide should not be used in individuals with known hypersensitivity or allergic reactions to benserazide or its components. Allergic reactions can range from mild skin rashes to severe, life-threatening allergic responses. 
• Narrow-angle glaucoma: benserazide may exacerbate the symptoms of narrow-angle glaucoma, a condition characterized by increased pressure within the eye. Therefore, it is contraindicated in individuals with this condition. 
• Pheochromocytoma: benserazide should not be used in patients with pheochromocytoma, a rare adrenal gland tumor that produces excessive amounts of adrenaline and other catecholamines. benserazide may lead to increased catecholamine levels and potentially dangerous cardiovascular effects in such individuals. 
• Severe cardiovascular disease: Patients with severe cardiovascular diseases, such as severe heart failure or recent myocardial infarction (heart attack), may be at increased risk of adverse effects if treated with benserazide. 
• Use of non-selective monoamine oxidase (MAO) inhibitors: benserazide should not be used concomitantly with non-selective MAO inhibitors, as this combination can lead to an increased risk of hypertensive crisis due to the inhibition of enzymes responsible for the breakdown of certain neurotransmitters. 
• Use of serotonin reuptake inhibitors (SSRIs): Combining benserazide with SSRIs may increase the risk of serotonin syndrome, a potentially life-threatening condition characterized by confusion, agitation, rapid heart rate, and increased body temperature. 

Caution: 

• Hypotension: benserazide can sometimes cause low blood pressure (hypotension), especially when starting treatment or increasing the dose. 
• Psychiatric disorders: Patients with a history of psychiatric disorders or depression may experience worsened symptoms while taking benserazide.  
• History of melanoma: Patients with a history of melanoma or at increased risk of developing melanoma may require careful monitoring while using benserazide.

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

benserazide acts as an aromatic L-amino acid decarboxylase (AADC) inhibitor. AADC is an enzyme in the body’s central nervous system (CNS) and peripheral tissues. In the CNS, AADC is essential for converting levodopa (L-DOPA) into dopamine, which helps alleviate the symptoms of Parkinson’s disease.  

benserazide prevents the premature conversion of levodopa to dopamine outside the brain by inhibiting AADC in peripheral tissues. This results in more levodopa reaching the brain, where it can be converted to dopamine and provide therapeutic benefits for Parkinson’s disease. 

Pharmacodynamics:  

Peripheral Decarboxylase Inhibition:  

• benserazide exerts its pharmacodynamic effect by acting as an inhibitor of the enzyme aromatic L-amino acid decarboxylase (AADC) in peripheral tissues. AADC converts levodopa (L-DOPA) into dopamine outside the central nervous system (CNS). This peripheral conversion leads to a reduced amount of levodopa reaching the brain, limiting its therapeutic effectiveness. 
• As a PDI, benserazide selectively inhibits AADC in the peripheral tissues, preventing the premature conversion of levodopa into dopamine before it crosses the blood-brain barrier. By inhibiting AADC, benserazide ensures that more levodopa reaches the brain, where it can be converted to dopamine, thus improving the treatment of Parkinson’s disease. 

Pharmacokinetics: 

Absorption 

benserazide is administered orally in the form of tablets or capsules. After ingestion, it is rapidly absorbed from the gastrointestinal tract. The absorption of benserazide primarily occurs in the small intestine. It is essential to note that benserazide is not intended to be used as a single agent; it is always co-administered with levodopa to enhance its therapeutic efficacy. 

Distribution 

benserazide is well-distributed throughout the body, including the central nervous system (CNS) and peripheral tissues. As a peripheral decarboxylase inhibitor (PDI), benserazide acts on peripheral tissues to inhibit the conversion of levodopa to dopamine before it reaches the brain. This enhances the availability of levodopa for conversion to dopamine within the CNS, where it exerts its therapeutic effect in Parkinson’s disease. 

Metabolism 

benserazide undergoes hepatic metabolism, mainly through enzymatic processes in the liver. The specific metabolic pathways involved in the metabolism of benserazide have yet to be extensively studied. However, the primary focus is on its peripheral decarboxylase inhibitory action rather than extensive hepatic metabolism. 

Elimination and Excretion 

After metabolism, the metabolites of benserazide are primarily eliminated through the kidneys via urine. Only a small fraction of the drug and its metabolites are excreted in the feces. 

Adminstartion

Administration: 

Oral administration 

It is administered in the form of tablets or capsules 

Patient Information Leaflet

Patient information leaflet 

Generic Name: benserazide 

Why do we use benserazide? 

benserazide is a medication primarily used in combination with levodopa for the treatment of Parkinson’s disease. Its primary role is to enhance the effectiveness of levodopa therapy by preventing its breakdown in the bloodstream before it reaches the brain.