Pregabalin

• oral – 30 – 90 minutes ⁴.
• all ROA’sroute of administration - where the drug gets into your body – 90 – 150 minutes ⁵.

• oral – 6 – 14 hours ⁴.
• all ROA’sroute of administration - where the drug gets into your body – 6 – 14 hours ⁵.

• all ROA’sroute of administration - where the drug gets into your body – 1 – 12 hours ⁵.

The pharmacological action of pregabalin is mediated by binding to the α2δ-1 site of voltage-gated calcium channels ⁶, ⁷. This site has also been referred to as the gabapentin receptor, as it is the target of the related substance gabapentin (also developed by Pfizer). Advantages to pregabalin over gabapentin include higher bioavailability and potency.

Although pregabalin is a chemical derivative of GABAGamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in your brain, meaning it slows your brain's functions. GABA is known for producing a calming effect., it displays no activity at any GABAGamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in your brain, meaning it slows your brain's functions. GABA is known for producing a calming effect. receptorsnerve endings that sense changes in the body More, including GABAA, GABAB and the benzodiazepine site. Pregabalin, despite its GABAGamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in your brain, meaning it slows your brain's functions. GABA is known for producing a calming effect. backbone, does not appear to alter GABAGamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in your brain, meaning it slows your brain's functions. GABA is known for producing a calming effect. levels in the brain, so its pharmacological activity is presumed to be unrelated to GABAGamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in your brain, meaning it slows your brain's functions. GABA is known for producing a calming effect. ⁸. Instead, it is its binding to the α2δ-1 site of voltage-gated calcium channels which appears to be the source of its subjective effects. By binding to this site, Pregabalin reduces the release of several excitatory neurotransmitters, including glutamate, substance P, acetylcholine and norepinephrine.

One study has also shown that pregabalin promotes deep sleep, thus enhancing sleep quality. This may be substantial because reductions in slow-wave sleep have been associated with anxiety and fibromyalgia ⁹. Also, an independent action of the gabapentin site on the neurogenesis of excitatory synapses has been discovered. The endogenousproduced within or caused by factors within the body. More neurochemical thrombospondin also binds to this site and is important for the generation of new excitatory synapses. Gabapentin and pregabalin, having a high affinity for this site, block this action and result in lower levels of excitatory synapses in animal models ⁷, ⁴.

Pregabalin is rapidly absorbed when administered on an empty stomach, with peak plasma concentrations occurring within 1 to 1.5 hours. Pregabalin oral bioavailability is estimated to be greater than or equal to 90%. The rate of pregabalin absorption is decreased when given with food, resulting in delay of approximately 3 hours to reach peak plasma concentrations, with peak levels themselves, decreased by about 25% to 30% ¹⁰. Administration with food, however, has no clinically significant effect on the extent of absorption ¹¹.

Pregabalin undergoes negligible metabolism in humans. In experiments using nuclear medicine techniques, it was revealed that approximately 98% of the radioactivity recovered in the urine was unchanged pregabalin. The primary metabolite is N-methyl pregabalin.

Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged substance. Renal clearance of pregabalin is 73 mL/minute ¹².

Pregabalin is well absorbed after oral administration. When an oral administration of pregabalin under fasting conditions is given, the pharmacokinetic parameters are as follows – tmaxthe time after administration of a drug when the maximum plasma concentration is reached; when the rate of absorption equals the rate of elimination. More = 1.5 hours; time to steady state = 24 – 48 hours ¹³.

Oral bioavailability = >90% (independent of dose) ¹³.

6.3 hours ¹³.

90% of the dose was recovered in the urine as the parent compound. The N-methylated derivative of pregabalin, the major metabolite was found in the urine and accounted for 0.9% of the dose ¹³.

Both rat and mouse oral acute LD50the amount of a material, given all at once, which causes the death of 50% (one half) of a group of test animals. The LD50 is one way to measure the short-term poisoning potential (acute toxicity) of a material have been established to be greater than 5000mg/kg. Rat IVintravenous More LD50the amount of a material, given all at once, which causes the death of 50% (one half) of a group of test animals. The LD50 is one way to measure the short-term poisoning potential (acute toxicity) of a material was also determined to be greater than 300mg/kg ¹⁴, ⁴.

Most common adverse reactions (≥5% and twice placeboA substance that has positive effects as a result of a patient's perception that it is beneficial rather than as a result of a causative ingredient. It is an inactive substance or preparation used as a control in an experiment or test to determine the effectiveness of a medicinal drug) are dizziness, somnolenceis a state of near-sleep, a strong desire for sleep, or sleeping for unusually long periods. More, dry mouth, oedemathe medical term for fluid retention in the body. Oedema often causes swelling in the feet and ankles. More, blurred vision, weight gain and thinking abnormal (primarily difficulty with concentration/attention) ¹³.

Tolerancethis is the process by which the receptors in your brain become habituated to the action of a drug. When tolerance is reached, more of the drug is required to achieve the same effect. With benzodiazepines, and probably with many other classes of drugs as well, tolerance is virtually always associated with some degree of physical dependence. If you find that you are experiencing tolerance, this is a clear warning sign that you may have formed a dependence. More will develop to the depressant effects within several days of continuous use. After cessation, the tolerancethis is the process by which the receptors in your brain become habituated to the action of a drug. When tolerance is reached, more of the drug is required to achieve the same effect. With benzodiazepines, and probably with many other classes of drugs as well, tolerance is virtually always associated with some degree of physical dependence. If you find that you are experiencing tolerance, this is a clear warning sign that you may have formed a dependence. More returns to baseline in 7 – 14 days. Withdrawal symptoms or rebound symptoms may occur after ceasing usage abruptly following a few weeks or longer of steady dosing and may necessitate a gradual dose reduction ⁴.

Pregabalin binds with high affinity to the alpha2-delta site (an auxiliary subunit of voltage-gated calcium channels) in central nervous systembrain and spinal cord tissues. Although the mechanism of action of pregabalin is unknown, results with genetically modified mice and with compounds structurally related to pregabalin (such as gabapentin) suggest that binding to the alpha2-delta subunit may be involved in pregabalin’s antinociceptive and antiseizure effects in animal models. in-vitrooutside the body, pregabalin reduces the calcium-dependent release of several neurotransmitters, possibly by modulation of calcium channel function. Studies also suggest that the descending noradrenergic and serotonergic pathways originating from the brainstem may be involved with the mechanism of pregabalin. Interestingly, although pregabalin is a structural derivative of inhibitory neurotransmitter GABAGamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in your brain, meaning it slows your brain's functions. GABA is known for producing a calming effect., it does not bind directly to GABAGamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in your brain, meaning it slows your brain's functions. GABA is known for producing a calming effect. or benzodiazepine receptorsnerve endings that sense changes in the body More. The sodium channels, opiate receptorsnerve endings that sense changes in the body More, and cyclooxygenase enzymes are not involved with the mechanism of pregabalin. It is also inactive at serotonin and dopamine receptorsnerve endings that sense changes in the body More and does not inhibit dopamine, serotonin, or noradrenaline reuptake ¹³.

Pregabalin can produce feelings of –

• euphoriafeelings of joy and happiness,
• relaxation,
• calmness ¹.

It can also enhance/increase the euphoric effects of other drugs, like opiates ¹.

Less commonly, pregabalin can cause –

• hallucinationswhere someone sees, hears, smells, tastes or feels things that don't exist outside of their mind,
• heart problems (including heart failure),
• depression,
• agitation,
• panic attacks ¹.

• muscle relaxation,
• physical euphoriaan intense feeling of pleasure and well-being More,
• motor control loss,
• pain relief,
• respiratory depressionslowing the drive and effectiveness of breathing More,
• sedationthe state of being relaxed or sleepy because of a drug More,
• seizure suppression,
• dizziness,
• muscle spasms ⁴.

• cognitive euphoriastate of intense well-being, happiness, and excitement More,
• dream potentiationcan be described as a cognitive component which increases the intensity, vividness and frequency of sleeping dream states. This effect also creates higher detail and definition within dreams alongside of an increase in the likelihood of one's dreams becoming lucid. More,
• empathy, love, and sociability enhancement,
• increased libido,
• increased music appreciation,
• motivation enhancement,
• amnesiainability to remember,
• anxiety suppression,
• decreased libido,
• disinhibition,
• information processing suppressioncan be described as a partial to complete suppression of a person's ability to process information and logically analyse a situation in an understandable and linear fashion. This is something which can result in states of stupor, indecisiveness, confusion and even irrational behaviour or delirium. More,
• thought deceleration ⁴.

• colour enhancement,
• acuity suppression,
• internal hallucinationsbest described as the perception of imagery and scenes which are experienced exclusively within a layer in front of one's open or closed eye vision and not seamlessly within the external environment around oneself. At lower levels, internal hallucinations begin with imagery which does not take up the entirety of one's visual field and is distinctively separate from its background. These can be described as spontaneous moving or still images of scenes, concepts, places, and anything one could imagine. They are manifested in varying levels of detail, ranging from ill-defined and cartoon-like in nature to completely realistic and beyond realism through seemingly impossible, non-euclidean geometric forms. They rarely hold their form for more than a few seconds before fading or shifting into another image. More ⁴.

• auditory distortion,
• auditory enhancement ⁴.

• constipationmeans that you're not passing stools regularly or you're unable to completely empty your bowels. More,
• vomiting,
• nausea,
• flatulenceexcessive wind, also known as 'farts',
• poor muscle control,
• trouble sleeping,
• weight gain,
• visual disturbances like blurred vision ¹.

It is recommended that prescribed pregabalin use is not stopped abruptly as it may cause anxiety, insomniadifficulty in going to sleep or in getting enough sleep, nausea, pain and sweating.

Substantial misuse of pregabalin has been reported. In view of this and in view of pregabalin known effects, it seems possible that dependence may develop in some regular users ¹.

• Like drinking and driving, driving while under the influence of drugs is illegal – with some drugs you can still be unfit to drive the day after using. You can get a heavy fine, be disqualified from driving or even go to prison ¹.