Products
Pregabalin is commercially available in capsule form and as an oral solution (Lyrica, generics). It was approved in the United States and EU in 2004 and in many countries in 2005.
Structure and properties
Pregabalin (C8H17NO2, Mr = 159.2 g/mol) exists as a white crystalline powder that is soluble in water. It was developed as a successor agent to gabapentin (Neurontin, generic) to improve its pharmacokinetic properties. Pregabalin is an isobutyl derivative of the neurotransmitter GABA and exists as an -enantiomer. The -enantiomer is pharmacologically inactive.
Effects
Pregabalin (ATC N03AX16) has analgesic, antiepileptic, antianxiety, and sedative properties. In the central nervous system, it reduces the release of various neurotransmitters such as glutamate, norepinephrine, and substance P, thereby decreasing neuronal excitability.
Mechanism of action
As with gabapentin, the effects are due to binding to the regulatory α2-δ-subunit of voltage-gated calcium channels of presynaptic neurons. These channels consist of 4 subunits and mediate the influx of calcium ions into neurons, leading to exocytosis of neurotransmitters and thus conduction of the action potential across the synapse. Binding of pregabalin reduces the influx of calcium ions through a conformational change (Figure). What are the differences from the precursor gabapentin? Pregabalin binds with higher affinity to calcium channels, has higher bioavailability, linear pharmacokinetics, and needs to be taken less frequently. Gabapentin is not indicated for anxiety disorders or for the treatment of fibromyalgia.
Indications
- Peripheral and central neuropathic pain (e.g., diabetic neuropathy, postherpetic neuralgia, spinal cord injury)
- Partial seizures with or without secondary generalization.
- Generalized anxiety disorder
In some countries, pregabalin is additionally approved for the treatment of fibromyalgia.
Dosage
According to the drug label. Capsules are usually taken two to three times daily, independent of meals. Treatment is started gradually and it is also recommended to gradually reduce the dose when stopping.
Abuse
Pregabalin can be abused as a sedating narcotic.
Contraindications
- Hypersensitivity
For complete precautions, see the drug label.
Interactions
Pregabalin has a low potential for pharmacokinetic drug-drug interactions because it is almost not metabolized and is excreted unchanged by the kidney. Because of its sedative properties, it may potentiate the effects of alcohol and lorazepam (Temesta, generics). Respiratory disturbances and coma have been reported with concomitant use of centrally depressant drugs. Other interactions have been described with opioids.
Adverse effects
The most common potential adverse effects include drowsiness, somnolence, and headache.
