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Gabapentin

Basic information Description Generic formulation Indications Dose titration Cautions Interactions Special populations Behavioural and cognitive effects in patients with epilepsy Psychiatric use Safety Related Supplier

Gabapentin Basic information

Product Name:
Gabapentin
CAS:
60142-96-3
MF:
C9H17NO2
MW:
171.24
EINECS:
262-076-3
Mol File:
60142-96-3.mol
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Gabapentin Chemical Properties

Melting point:
162°C
Boiling point:
314.4±15.0 °C(Predicted)
Density 
1.058±0.06 g/cm3(Predicted)
Flash point:
9℃
storage temp. 
Desiccate at +4°C
solubility 
H2O: 10 mg/mL
pka
pKa1 (25°) 3.68; pKa2 10.70
form 
solid
color 
off-white
Merck 
14,4319
BRN 
2359739
InChIKey
UGJMXCAKCUNAIE-UHFFFAOYSA-N
CAS DataBase Reference
60142-96-3(CAS DataBase Reference)
EPA Substance Registry System
Cyclohexaneacetic acid, 1-(aminomethyl)- (60142-96-3)
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Safety Information

Hazard Codes 
T,Xi,F
Risk Statements 
61-36/37/38-39/23/24/25-23/24/25-11
Safety Statements 
53-26-36/37/39-45-36-36/37-16
RIDADR 
UN1230 - class 3 - PG 2 - Methanol, solution
WGK Germany 
3
RTECS 
GU6496000
HazardClass 
IRRITANT
HS Code 
29224999
Hazardous Substances Data
60142-96-3(Hazardous Substances Data)

MSDS

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Gabapentin Usage And Synthesis

Description

Gabapentin is a second- generation antiepileptic drug (AED) known under the proprietary brand name of Neurontin® (Pfizer, New York, NY) in the UK and USA.

Generic formulation

MHRA/ CHM advice to minimize risk when switching patients with epilepsy between different manufacturers’ products (including generic products):

  • It is usually unnecessary to ensure that patients are maintained on a specific manufacturer’s product unless there are specific concerns, such as patient anxiety and risk of confusion/ dosing error.

Indications

Epilepsy: monotherapy or adjunctive therapy of focal seizures with or without secondary generalization. Recommendations summarized from NICE (2012)

  • Seizure types: adjunctive (focal seizures), contraindicated (generalized tonic- clonic seizures generalized tonic- clonic seizures if there are absence or myoclonic seizures, or if juvenile myoclonic epilepsy is suspected, tonic/ atonic seizures, absence seizures, myoclonic seizures).
  • Epilepsy types: adjunctive (benign epilepsy with centrotemporal spikes, Panayiotopoulos syndrome, late- onset childhood occipital epilepsy), contraindicated (absence syndromes, juvenile myoclonic epilepsy, idiopathic generalized epilepsy, Dravet syndrome, Lennox– Gastaut syndrome)
  •  Psychiatry— treatment of anxiety disorders (unlicensed); treatment of alcohol withdrawal symptoms (unlicensed).
  •  Neurology— treatment of neuropathic pain and restless leg syndrome (unlicensed) and prophylaxis of migraine (unlicensed).

Dose titration

Monotherapy or adjunctive therapy
300 mg od for day 1300 mg bd for day 2300 mg td for day 3 (or 300 mg td for day 1), then increased by 300 mg every 2– 3 days, divided into three doses; usual maintenance 900– 3600 mg daily, divided into three doses (max. 4800 mg daily) If gabapentin has to be discontinued, it is recommended this should be done gradually over a minimum of 1 week, independent of the indication.

Cautions

  • Patients with a history of psychotic illness.
  • Patients with mixed seizures (including absences).
  • Patients with diabetes mellitus.
  • Elderly patients.

Interactions

With AEDs
Nil.

With other drugs

  • Patients who require concomitant treatment with opioids should be carefully observed for signs of respiratory depression and/ or sedation, and the dose of gabapentin or opioid should be reduced appropriately
  • Co-administration of gabapentin with antacids containing aluminium and magnesium, reduces gabapentin bioavailability up to 24%, and it is therefore recommended that gabapentin be taken at the earliest 2 hours following antacid administration

With alcohol/food
There are no known specific interactions between alcohol and gabapentin and there are no specific foods that must be excluded from diet when taking gabapentin.

Special populations

Renal impairment
Reduce maintenance dose according to degree of reduction in creatinine clearance.

Pregnancy

  • The dose of gabapentin should be monitored carefully during pregnancy and after birth, and adjustments made on a clinical basis.
  • No definite conclusion can be made as to whether gabapentin is associated with an increased risk of congenital malformations when taken during pregnancy. Gabapentin should not be used during pregnancy unless the potential benefit to the mother clearly outweighs the potential risk to the foetus.
  • Gabapentin is excreted in human milk. Because the effect on the breastfed infant is unknown, gabapentin should be used in breastfeeding mothers with caution and only if the benefits clearly outweigh the risks.

Behavioural and cognitive effects in patients with epilepsy

Gabapentin has a relatively favourable behavioural profile, although paradoxical hyperactivity, irritability and aggression have been occasionally reported, especially in patients with severe intellectual disabilities. The cognitive profile of gabapentin is equally favourable, as this AED has been associated with only minor cognitive difficulties (mainly in the attention domain).

Psychiatric use

Although gabapentin has no approved indications in psychiatry, it has shown efficacy in the treatment of anxiety disorders, especially social phobia. Other offlabel uses include other anxiety disorders (panic disorder, post- traumatic stress disorder), alcohol dependence and withdrawal, behavioural and psychological symptoms of dementia, and aggression. Gabapentin has also been proposed to be useful in the maintenance treatment of bipolar disorder as adjunctive therapy.

Description

Gabapentin was introduced in 1993 in the UK and early 1994 in the USA as an adjunctive therapy in the treatment of refractory partial seizures and secondarily generalized tonic-clonic seizures. Although being a lipophilic analog of the neurotransmitter GABA, gabapentin appears to exert its anticonvulsive function by a GABA receptor independent mechanism, possibly involving the L-system amino acid transporter protein. Gabapentin easily crosses the blood brain barrier and exhibits a favorable pharmacokinetic profile with high tolerability. It does not interfere with the metabolism of other concomitant administered antiepileptic drugs, thus having a low potential for drug interactions. Studies are currently underway for the use of gabapentin as mono-therapy for the treatment of various seizures.

Chemical Properties

White Crystalline Solid

Originator

Warner-Lambert (U.S.A.)

Uses

Amino acid structurally related to γ-Aminobutyric Acid (GABA), designed to cross the blood brain barrier. Used as an anticonvulsant.

Uses

antipsychotic, 5HT2A antagonist

Uses

selective H1-receptor antagonist

Uses

For the treatment of adult Restless Legs Syndrome (RLS) and postherpetic neuralgia (PHN).

Definition

ChEBI: A gamma-amino acid that is cyclohexane substituted at position 1 by aminomethyl and carboxymethyl groups. Used for treatment of neuropathic pain and restless legs syndrome.

Indications

Gabapentin (Neurontin) significantly decreases pain scores and sleep interference associated with PHN. An initial dose of 300 mg/day is increased over 4 weeks (900, 1,800, 2,400, 3,600 mg/day divided t.i.d.) until efficacy is obtained or side effects become intolerable.

brand name

Neurontin (ParkeDavis); Neurontin (Pfizer).

Biological Functions

Gabapentin (Neurotonin) was initially designed to be a rigid analogue of GABA. When it was discovered to have antiepileptic properties, it was assumed that this activity was related to a GABAergic mechanism. However, subsequent studies have failed to show any GABAergic activity of gabapentin. Although it has not yet been possible to ascribe any definite mechanism to its antiepileptic activity, there is recent evidence that it may function as an agonist at GABAB receptors in the brain.
Gabapentin is recommended as adjunctive therapy in the treatment of partial seizures in adults.When used with other drugs, it appears to be an effective AED; it is usually not effective when employed alone for patients with severe seizures.
Gabapentin is generally well tolerated, with somnolence, dizziness, and ataxia the most commonly reported adverse effects. A low incidence of potentially serious side effects and no significant allergic reactions have been reported.

General Description

Gabapentin and its closely related analog pregabalin,(S)-3-isobutyl-GABA, are broad-spectrum anticonvulsantswith multiple mechanisms of action.24,51 Inaddition to modulating calcium influx and stimulateGABA biosynthesis as discussed earlier, they also competefor the biosynthesis of L-glutamic acid because oftheir structural similarity to L-leucine.51 Gabapentin andpregabalin have very little liability for causing metabolicbaseddrug–drug interactions, particularly when used incombination with other AEDs because they are not metabolizedin humans. More than 95% of the drug is excretedunchanged through the kidneys. However, there are somedifferences in their bioavailability. Unlike gabapentin,which exhibits 60% bioavailability when given in lowdoses because of intestinal uptake by a saturable smallneutral L-amino acid transporter, the absorption of pregabalinis almost complete (98%) and exhibits an ideal linear pharmacokinetic profile.24 This high bioavailability of pregabalincan be attributed to its closer structure similarity tothe essential amino acid, L-leucine.

Biological Activity

Anticonvulsant with several possible mechanisms of action. Increases GABA in the brain and binds to a novel site associated with voltage-sensitive Ca 2+ channels. Prevents neuronal death and is antinociceptive and anxiolytic.

Side effects

Dose-limiting adverse effects include somnolence, dizziness, ataxia, peripheral edema, and infection (22).

Veterinary Drugs and Treatments

Gabapentin may be useful as adjunctive therapy for refractory or complex partial seizures, or in the treatment of chronic pain in dogs or cats.

Gabapentin Preparation Products And Raw materials

Raw materials

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GabapentinSupplierMore

Jiangxi Synergy Pharmaceutical Co. Ltd. Gold
Tel:
021-62886322;0795-4605771
Email:
info@jxsynergy.com;info@jxsynergy.com
Changzhou Boren Chemical Technology Co., Ltd. Gold
Tel:
Email:
sales@borenchem.cn
J & K SCIENTIFIC LTD.
Tel:
010-82848833- ;010-82848833-
Email:
jkinfo@jkchemical.com;market6@jkchemical.com
Meryer (Shanghai) Chemical Technology Co., Ltd.
Tel:
21-61259100-
Email:
sh@meryer.com
INTATRADE GmbH
Tel:
+49 3493/605464
Email:
sales@intatrade.de
Basic information Description Generic formulation Indications Dose titration Cautions Interactions Special populations Behavioural and cognitive effects in patients with epilepsy Psychiatric use Safety Related Supplier