Biomaterial Database

The interaction between gabapentin and amitriptyline in the rat formalin test after systemic administration. 2002

Caroline E Heughan, and Jana Sawynok

Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.

We examined the effects of systemically administered gabapentin on flinching and biting/licking behaviors produced by 2.5% formalin in the rat, compared these with those of amitriptyline, and determined the effects of combinations of gabapentin with amitriptyline. Gabapentin produced a dose-related inhibition of Phase 2, but not Phase 1, flinching and biting/licking behaviors. In contrast, amitriptyline produced an increase in Phase 2 flinching behaviors while simultaneously decreasing biting/licking behaviors. Fifty percent effective dose (ED50) values against biting/licking behaviors were 22.9 +/- 1.3 mg/kg and 8.5 +/- 1.3 mg/kg for gabapentin and amitriptyline, respectively. Combinations of increasing fractional increments of ED50 doses of gabapentin and amitriptyline produced an additive effect against biting/licking behaviors, as revealed by isobolographic analysis. These increments had no effect on flinching behaviors except at the ED25 + ED25 doses, at which flinching was increased, again revealing additivity between the two drugs. Flinching behaviors in rats do not reflect the analgesic properties of systemically administered amitriptyline observed in humans and may not be useful for predicting an effect of combinations of drugs with amitriptyline. Biting/licking behaviors do reflect analgesic properties for both drugs and may be more useful in this regard. CONCLUSIONS By use of the rat formalin test, a model of persistent pain, we examined the effect of a combination of amitriptyline and gabapentin, which are used to treat chronic pain in humans. The drug combination produced additive analgesia against one outcome, but another outcome was more ambiguous.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D010146	Pain	An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.	Suffering, Physical,Ache,Pain, Burning,Pain, Crushing,Pain, Migratory,Pain, Radiating,Pain, Splitting,Aches,Burning Pain,Burning Pains,Crushing Pain,Crushing Pains,Migratory Pain,Migratory Pains,Pains, Burning,Pains, Crushing,Pains, Migratory,Pains, Radiating,Pains, Splitting,Physical Suffering,Physical Sufferings,Radiating Pain,Radiating Pains,Splitting Pain,Splitting Pains,Sufferings, Physical
D010147	Pain Measurement	Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies.	Analgesia Tests,Analogue Pain Scale,Formalin Test,McGill Pain Questionnaire,Nociception Tests,Pain Assessment,Pain Intensity,Pain Severity,Tourniquet Pain Test,Visual Analogue Pain Scale,Analog Pain Scale,Assessment, Pain,McGill Pain Scale,Visual Analog Pain Scale,Analgesia Test,Analog Pain Scales,Analogue Pain Scales,Formalin Tests,Intensity, Pain,Measurement, Pain,Nociception Test,Pain Assessments,Pain Intensities,Pain Measurements,Pain Questionnaire, McGill,Pain Scale, Analog,Pain Scale, Analogue,Pain Scale, McGill,Pain Severities,Pain Test, Tourniquet,Questionnaire, McGill Pain,Scale, Analog Pain,Scale, Analogue Pain,Scale, McGill Pain,Severity, Pain,Test, Analgesia,Test, Formalin,Test, Nociception,Test, Tourniquet Pain,Tests, Nociception,Tourniquet Pain Tests
D003509	Cyclohexanecarboxylic Acids	Carboxylic acid derivatives of cyclohexane.	Acids, Cyclohexanecarboxylic
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004357	Drug Synergism	The action of a drug in promoting or enhancing the effectiveness of another drug.	Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D004359	Drug Therapy, Combination	Therapy with two or more separate preparations given for a combined effect.	Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D005557	Formaldehyde	A highly reactive aldehyde gas formed by oxidation or incomplete combustion of hydrocarbons. In solution, it has a wide range of uses: in the manufacture of resins and textiles, as a disinfectant, and as a laboratory fixative or preservative. Formaldehyde solution (formalin) is considered a hazardous compound, and its vapor toxic. (From Reynolds, Martindale The Extra Pharmacopoeia, 30th ed, p717)	Formalin,Formol,Methanal,Oxomethane
D005680	gamma-Aminobutyric Acid	The most common inhibitory neurotransmitter in the central nervous system.	4-Aminobutyric Acid,GABA,4-Aminobutanoic Acid,Aminalon,Aminalone,Gammalon,Lithium GABA,gamma-Aminobutyric Acid, Calcium Salt (2:1),gamma-Aminobutyric Acid, Hydrochloride,gamma-Aminobutyric Acid, Monolithium Salt,gamma-Aminobutyric Acid, Monosodium Salt,gamma-Aminobutyric Acid, Zinc Salt (2:1),4 Aminobutanoic Acid,4 Aminobutyric Acid,Acid, Hydrochloride gamma-Aminobutyric,GABA, Lithium,Hydrochloride gamma-Aminobutyric Acid,gamma Aminobutyric Acid,gamma Aminobutyric Acid, Hydrochloride,gamma Aminobutyric Acid, Monolithium Salt,gamma Aminobutyric Acid, Monosodium Salt
D000077206	Gabapentin	A cyclohexane-gamma-aminobutyric acid derivative that is used for the treatment of PARTIAL SEIZURES; NEURALGIA; and RESTLESS LEGS SYNDROME.	1-(Aminomethyl)cyclohexaneacetic Acid,Apo-Gabapentin,Convalis,Gabapentin Hexal,Gabapentin Stada,Gabapentin-Ratiopharm,Neurontin,Novo-Gabapentin,PMS-Gabapentin,Apo Gabapentin,ApoGabapentin,Gabapentin Ratiopharm,Novo Gabapentin,NovoGabapentin