by egpat 23 May 2024
Gabapentin and pregabalin both belong to the same category, and they are classified as anti-epileptic agents. Both of these drugs can be used in the treatment of partial-onset seizures, but they are not equivalent. Gabapentin is available under various brand names, and among them, Neurontin is one of the brands that is well known. Pregabalin is well familiar with its brand name, Lyrica. Interestingly, we can find a single word in both of these drug names; we can find the term "GABA" in both of these drugs. So both gabapentin and pregabalin are GABA derivatives.
GABA is an important neurotransmitter in the CNS, which is nothing but gamma-aminobutyric acid. Since both of these drugs have GABA incorporated into their structures, these drugs are called GABApentinoids. Even though they are classified as antiepileptics, they are mainly used to control neuropathic pain. So in the management of neuropathic pain, gabapentin and pregabalin are the two important drugs; however, they are not equivalent.
Both gabapentin and pregabalin work in a similar way; they can act on the neurons, particularly the excitatory neurons, which are storing the glutamate. The release of glutamate is controlled by one of the ion-channel voltage-gated calcium channels. This calcium channel opens based on the voltage within the presynaptic neurons. So when an impulse reaches the presynaptic neuron, these voltage-gated calcium channels are open so calcium can enter, which produces depolarization and results in the release of glutamate. This glutamate can bind to AMPA receptors, resulting in post-synaptic excitation.
In this way, glutamate produces excitation of the neurons, but when this excitation is uncontrolled and excessive, it may lead to various disorders like epilepsy, or else it can produce some neuronal dysfunction resulting in increased nociception, leading to neuropathic pain. In such conditions, gabapentin and pregabalin can control this neuronal activity. The voltage-gated calcium channels that play an important role in the release of glutamate have an extra-pocket, Alpha2 delta site.
Both pregabalin and gabapentin can bind to this Alpha2 delta site, thereby inhibiting the activity of voltage-gated calcium channels. Now, when these channels are not open, glutamate is not released, so this reduces glutamate transmission, thereby reducing neuronal excitability. In this way, both gabapentin and pregabalin act in a similar way by inhibiting the activity of voltage-gated calcium channels.
So this is the first similarity between gabapentin and pregabalin; even though they have the term GABA in their names, they're not affecting the GABA transmission.
At this point, gabapentin and pregabalin differ. Gabapentin is slowly absorbed through the small intestine, whereas pregabalin is rapidly absorbed. The rate of absorption is somewhat slower in the case of gabapentin. Another important thing is that gabapentin shows saturation kinetics, which means that when the dose of gabapentin is increased, the rate of absorption is not proportionally increased.
Therefore, even at higher doses, gabapentin doesn't show high absorption. This is because gabapentin is absorbed by a carrier-mediated mechanism. When all these carriers are saturated, the absorption of gabapentin is reduced.
On the other hand, pregabalin is better absorbed, and the absorption of pregabalin is not affected by the food. So at this point, pregabalin shows some advantage because it has better absorption and does not show any saturation kinetics.
Gabapentin can be used for the treatment of partial-onset seizures; that's why it is classified as an anti-epileptic agent. It can be used as an adjuvant along with other drugs. Apart from this clinical use, it is mainly used in other conditions like post-herpetic neuralgia, where neuronal pain is produced after any herpes infection. Similarly, it can be used for the treatment of neuropathic pain, where excessive neuronal activity increases nociception.
Pregabalin is also used for the same purpose; it can be used for partial-onset seizures, post-herpetic neuralgia, and neuropathic pain. Apart from these clinical indications, pregabalin can be used in the management of fibromyalgia. In conditions like diabetic neuropathy, both gabapentin and pregabalin can be used, but pregabalin is more effective in the treatment of diabetic neuropathy.
On the other hand, gabapentin can be used for conditions like restless leg syndrome, which is a condition where a patient has the desire to move the legs. In such conditions, gabapentin can be used for off-label purposes.
Both gabapentin and pregabalin act in a similar way; they can bind to the alpha-2 delta site of voltage-gated calcium channels. However, the binding affinity is somewhat different. Pregabalin shows more binding affinity, so it can be used at a low dose to control neuropathic pain.
Gabapentin is available as a capsule as well as a tablet. It can be started initially at a dose of 300 mg per day, and the maximum dose can be achievable based on the clinical conditions. It is variable from 1800 mg to 2,400 mg per day, and it can be given in divided doses three times a day.
Pregabalin is also available as a capsule or tablet, and the initial dose is variable from 50 to 75 mg based on the clinical indication, and the maximum dose is also variable from 450 mg to 600 mg per day.
So the dose of pregabalin is somewhat lower because this drug is more potent compared with gabapentin. Gabapentin should be given at a higher dose because it is somewhat less absorbed compared with pregabalin.
Both gabapentin and pregabalin show similar side effects. They act centrally to produce various side effects like dizziness, drowsiness, somnolence, and sleepiness in people. They can also produce some blurred vision. All these common side effects can be observed with both gabapentin and pregabalin.
But few of the side effects are more pronounced with pregabalin; it can produce some dry mouth, peripheral edema, and weight gain. On the other hand, a few other side effects of gabapentin include nystagmus, or involuntary movements of the eye. It can also produce some hyperkinesia, or jerky motor movements. Dry mouth is more troublesome with pregabalin, and involuntary movements are more troublesome with gabapentin.
In the treatment of neuropathic pain, which drug shows more analgesic activity? Gabapentin should be used at a high dose, whereas pregabalin is used at a low dose due to its higher potency. In addition, pregabalin can show more analgesic activity even at low doses compared with gabapentin.
At this point, both gabapentin and pregabalin act in a similar way. Both of these drugs are addictive at higher doses, and they should not be stopped suddenly. They can produce some withdrawal effects when they are stopped suddenly. Their doses should be slowly tapered in order to avoid withdrawal effects.
These are the few similarities and differences between gabapentin and pregabalin. In terms of analgesic activity and potency, pregabalin shows more advantages, but in terms of side effects, gabapentin is somewhat more tolerated, as pregabalin produces some dry mouth, peripheral edema, and weight gain.