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药品详细

Pregabalin(普瑞巴林)

化学结构式图
中文名
普瑞巴林
英文名
Pregabalin
分子式
C8H17NO2
化学名
(3S)-3-(aminomethyl)-5-methylhexanoic acid
分子量
Average: 159.2261
Monoisotopic: 159.125928793
CAS号
148553-50-8
ATC分类
N03A 未知
药物类型
small molecule
阶段
illicit, approved
商品名
同义名
基本介绍

Pregabalin is an anticonvulsant drug used for neuropathic pain, as an adjunct therapy for partial seizures, and in generalized anxiety disorder. It was designed as a more potent successor to gabapentin. Pregabalin is marketed by Pfizer under the trade name Lyrica. It is considered to have a dependence liability if misused, and is classified as a Schedule V drug in the U.S. [Wikipedia]

生产厂家
  • Cp pharmaceuticals cv
  • Pfizer inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. : Schedules of controlled substances: placement of pregabalin into schedule V. Final rule. Fed Regist. 2005 Jul 28;70(144):43633-5. Pubmed
  2. Su TZ, Feng MR, Weber ML: Mediation of highly concentrative uptake of pregabalin by L-type amino acid transport in Chinese hamster ovary and Caco-2 cells. J Pharmacol Exp Ther. 2005 Jun;313(3):1406-15. Epub 2005 Mar 15. Pubmed
  3. Li Z, Taylor CP, Weber M, Piechan J, Prior F, Bian F, Cui M, Hoffman D, Donevan S: Pregabalin is a potent and selective ligand for alpha(2)delta-1 and alpha(2)delta-2 calcium channel subunits. Eur J Pharmacol. 2011 Sep 30;667(1-3):80-90. doi: 10.1016/j.ejphar.2011.05.054. Epub 2011 Jun 1. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Amino Acids
  • Carboxylic Acids and Derivatives
Substructures
  • Amino Acids
  • Hydroxy Compounds
  • Acetates
  • Aliphatic and Aryl Amines
  • Carboxylic Acids and Derivatives
适应症
药理
Indication Pregabalin is used for the management of neuropathic pain associated with diabetic peripheral neuropathy or spinal cord injury, and postherpetic neuralgia. It is also used as adjunctive therapy for adult patients with partial onset seizures and management of fibromyalgia.
Pharmacodynamics Pregabalin is a new anticonvulsant drug indicated as an add on therapy for partial onset seizures and for certain types of neuropathic pain. It was designed as a more potent successor to a related drug, gabapentin. Pregabalin binds to the alpha2-delta subunit of the voltage-gated calcium channel in the central nervous system. While pregabalin is a structural derivative of the inhibitory neurotransmitter gamma- aminobutyric acid (GABA), it does not bind directly to GABAA, GABAB, or benzodiazepine receptors, does not augment GABAA responses in cultured neurons, does not alter rat brain GABA concentration or have acute effects on GABA uptake or degradation. However, in cultured neurons prolonged application of pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport. Pregabalin does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity. It is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.
Mechanism of action Pregabalin binds with high affinity to the alpha2-delta site (an auxiliary subunit of voltage-gated calcium channels) in central nervous system 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 vitro, 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 gamma-aminobutyric acid (GABA), it does not bind directly to GABA or benzodiazepine receptors. The sodium channels, opiate receptors, and cyclooxygenase enzymes are not involved with the mechanism of pregabalin. It is also inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.
Absorption Pregabalin is well absorbed after oral administration. When an oral administration of pregabalin under fasting conditions is given, the pharmacokinetic parameters are as follows: Tmax = 1.5 hours; Oral bioavailability = >90% (independent of dose); Time to steady state = 24-48 hours. It is also a substrate for the L-type transport system.
Volume of distribution

Apparent volume of distribution, oral administration = 0.5 L/kg.
Pregabalin has been shown to cross the placenta in rats and is present in the milk of lactating rats.
Protein binding Pregabalin does not bind to plasma proteins.
Metabolism
Pregabalin undergoes negligible metabolism in humans.
Route of elimination 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. Pregabalin (S-enantiomer) did not undergo racemization to the R-enantiomer.
Half life 6.3 hours
Clearance

Renal clearance, healthy subjects = 67.0 – 80.9 mL/min. Because pregabalin is not bound to plasma protein, this rate suggests the involvement of renal tubular reabsorption.
Toxicity Most common adverse reactions (≥5% and twice placebo) are dizziness, somnolence, dry mouth, edema, blurred vision, weight gain and thinking abnormal (primarily difficulty with concentration/attention).
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
water solubility Freely soluble FDA label
logP -1.35 FDA label
pKa 4.2 and 10.6 FDA label
Predicted Properties
Property Value Source
water solubility 1.13e+01 g/l ALOGPS
logP -1.4 ALOGPS
logP -1.3 ChemAxon
logS -1.1 ALOGPS
pKa (strongest acidic) 4.8 ChemAxon
pKa (strongest basic) 10.23 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 63.32 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 43.68 ChemAxon
polarizability 18.08 ChemAxon
药物相互作用
Drug Interaction
Triprolidine The CNS depressants, Triprolidine and Pregabalin, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
食物相互作用
  • Avoid alcohol (may increase CNS effects).
  • When taken with food, Cmax decreases, while Tmax is prolonged. Despite these observations, the total absorption of pregabalin is not effected to a clinically relevant degree. Pregabalin can be taken with or without food.

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