Parkinson's Disease Medications and Adrenergic Neurotransmitters

Parkinson's Disease: Pharmacological Treatments

The primary pharmacological treatment for Parkinson's disease focuses on replenishing dopamine, the neurotransmitter deficient in the disease, and managing associated symptoms. Levodopa, often combined with carbidopa, is the cornerstone of treatment, alongside dopamine agonists, MAO-B inhibitors, COMT inhibitors, and anticholinergic agents.

Key Medications for Parkinson's Disease

1. Levodopa

   Levodopa is a dopamine precursor that can cross the blood-brain barrier and is converted into dopamine in the brain.

   It is typically combined with carbidopa, which inhibits the breakdown of levodopa before it reaches the brain, reducing side effects and improving efficacy.

   Levodopa is effective in improving motor symptoms like slowness, stiffness, and tremor.

2. Dopamine Agonists

   These drugs mimic the action of dopamine by directly stimulating dopamine receptors.

   They can be used as an initial treatment or in combination with levodopa to manage symptoms and reduce fluctuations.

   Examples include pramipexole and ropinirole.

3. MAO-B Inhibitors (Monoamine Oxidase B Inhibitors)

   MAO-B inhibitors prevent the breakdown of dopamine in the brain, increasing its availability.

   They can be used as a monotherapy or in combination with other medications.

   Examples include selegiline and rasagiline.

4. COMT Inhibitors (Catechol-O-methyltransferase Inhibitors)

   COMT inhibitors inhibit the enzyme that breaks down levodopa, prolonging its effect and reducing "wearing off" at the end of the dose.

   They are often used as adjunctive therapy with levodopa.

5. Anticholinergic Agents

   Anticholinergic medications can help manage tremor, rigidity, and dystonia, but their effectiveness is less for slowness (bradykinesia).

   They can also cause side effects like dry mouth, blurred vision, and cognitive impairment.

   Examples include trihexyphenidyl and benztropine.

6. Other Medications for Parkinson's

   • Amantadine: Can improve motor symptoms, especially in early stages of the disease.
   • Apomorphine: Subcutaneous injection for acute "off" periods.
   • Non-Motor Symptoms: Medications like antidepressants and cholinesterase inhibitors may be used to address non-motor symptoms like depression and dementia.

Adrenergic Neurotransmitters and Receptors

Adrenergic Neurotransmitters are chemical messengers released by Adrenergic Neurons, which primarily act on adrenergic receptors (alpha-beta receptors) in the Sympathetic Nervous System. These neurotransmitters are involved in "fight or flight" responses like increasing heart rate, blood pressure, and energy availability. They are also known as Catecholamines.

Main Adrenergic Neurotransmitters

• Dopamine
• Norepinephrine
• Epinephrine

Understanding Each Neurotransmitter

• Dopamine

  It is the first catecholamine in the synthesis chain.

  It acts on dopaminergic receptors (D1, D2).

  It has mild action on β1 and α1 receptors at higher doses. It plays an important role in renal vasodilation, CNS functions (mood, movement), and is a precursor to norepinephrine.

• Norepinephrine

  Also known as Noradrenaline.

  It is the primary neurotransmitter released by sympathetic postganglionic neurons.

  It acts mainly on α1, α2, and β1 receptors.

  Primary functions include:

  • Increases heart rate and contractility (β1)
  • Vasoconstriction (α1) - increases blood pressure

• Epinephrine

  Also known as Adrenaline.

  It acts on α1, α2, β1, and β2 receptors.

  Functions:

  • Increases Heart Rate and Cardiac Output (β1)
  • Bronchodilation (β2)
  • Vasoconstriction (α1) and vasodilation in skeletal muscle

Steps in Catecholamine Synthesis

1. First, Phenylalanine is converted into Tyrosine by the enzyme "Phenylalanine Hydroxylase."
2. Tyrosine is converted into DOPA by the enzyme "Tyrosine Hydroxylase."
3. DOPA is then converted to Dopamine by the enzyme "DOPA Decarboxylase."
4. Dopamine is then converted to Norepinephrine by the enzyme "Dopamine β-hydroxylase."
5. Norepinephrine is then finally converted to Epinephrine by the enzyme "N-methyltransferase."

Adrenergic Receptors

Adrenergic Receptors are a class of G protein-coupled receptors (GPCRs) that are targeted by catecholamines, i.e., norepinephrine and epinephrine.

These receptors mediate the physiological response of the sympathetic nervous system and are involved in a wide range of processes, including heart rate regulation, smooth muscle contraction, or relaxation, etc.

Types of Adrenergic Receptors

Adrenergic Receptors are broadly classified into two main types:

1. Alpha (α) adrenergic receptors
2. Beta (β) adrenergic receptors

Detailed Adrenergic Receptor Types

• Alpha (α) Adrenergic Receptors

  They are mainly responsible for smooth muscle contraction and vasoconstriction.

  They are of two types:

  • α1 Receptors
  • α2 Receptors

• Beta (β) Adrenergic Receptors

  They usually cause smooth muscle relaxation and increase heart activity.

  They are of 3 types:

  • β1 Receptors
  • β2 Receptors
  • β3 Receptors