Potentiation of morphine antinociception by monoamine reuptake inhibitors in the rat spinal cord. 1985

Yetunde O Taiwo, and Annette Fabian, and Christopher J Pazoles, and Howard L Fields
Departments of Neurology and Physiology, University of California, San Francisco, CA 94143 USA Central Research Division, Pfizer, Inc., Groton, CT 06340 U.S.A.

Potentiation of the antinociceptive effects of morphine by the tricyclic antidepressants was assayed in awake restrained rats using the tail-flick test. Intrathecally administered amitriptyline, desipramine or sertraline at doses that had no effect themselves (25-30 micrograms) potentiated a subthreshold parenteral dose of morphine (0.5 mg/kg). The morphine potentiating effect of amitriptyline was prevented by prior administration of parachlorophenylalanine (PCPA). This effect of PCPA was not restored by 5-hydroxytryptophan (5-HTP) but was restored when the animals were left for 14 days to replete. The morphine potentiating effects of amitriptyline, desipramine and sertraline were blocked by intrathecal administration of low doses of the serotonin antagonist methysergide and the alpha-adrenergic antagonists yohimbine and phentolamine but not by the beta-adrenergic antagonist propranolol. The results are consistent with the hypothesis that the potentiation of morphine's antinociceptive effect by tricyclic antidepressants depends on activation of both spinopetal serotonin and adrenergic neurons.

UI MeSH Term Description Entries
D008297 Male Males
D009020 Morphine The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. Morphine Sulfate,Duramorph,MS Contin,Morphia,Morphine Chloride,Morphine Sulfate (2:1), Anhydrous,Morphine Sulfate (2:1), Pentahydrate,Oramorph SR,SDZ 202-250,SDZ202-250,Chloride, Morphine,Contin, MS,SDZ 202 250,SDZ 202250,SDZ202 250,SDZ202250,Sulfate, Morphine
D009619 Nociceptors Peripheral AFFERENT NEURONS which are sensitive to injuries or pain, usually caused by extreme thermal exposures, mechanical forces, or other noxious stimuli. Their cell bodies reside in the DORSAL ROOT GANGLIA. Their peripheral terminals (NERVE ENDINGS) innervate target tissues and transduce noxious stimuli via axons to the CENTRAL NERVOUS SYSTEM. Pain Receptors,Receptors, Pain,Nociceptive Neurons,Neuron, Nociceptive,Neurons, Nociceptive,Nociceptive Neuron,Nociceptor,Pain Receptor
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D003891 Desipramine A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholinergic activity, through its affinity to muscarinic receptors. Desmethylimipramine,Apo-Desipramine,Demethylimipramine,Desipramine Hydrochloride,Norpramin,Novo-Desipramine,Nu-Desipramine,PMS-Desipramine,Pertofran,Pertofrane,Pertrofran,Petylyl,Ratio-Desipramine,Apo Desipramine,Hydrochloride, Desipramine,Novo Desipramine,Nu Desipramine,PMS Desipramine,Ratio Desipramine
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
D000639 Amitriptyline Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antagonize cholinergic and alpha-1 adrenergic responses to bioactive amines. Amineurin,Amitrip,Amitriptylin Beta,Amitriptylin Desitin,Amitriptylin RPh,Amitriptylin-Neuraxpharm,Amitriptyline Hydrochloride,Amitrol,Anapsique,Apo-Amitriptyline,Damilen,Domical,Elavil,Endep,Laroxyl,Lentizol,Novoprotect,Saroten,Sarotex,Syneudon,Triptafen,Tryptanol,Tryptine,Tryptizol,Amitriptylin Neuraxpharm,Apo Amitriptyline,Desitin, Amitriptylin,RPh, Amitriptylin
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000929 Antidepressive Agents, Tricyclic Substances that contain a fused three-ring moiety and are used in the treatment of depression. These drugs block the uptake of norepinephrine and serotonin into axon terminals and may block some subtypes of serotonin, adrenergic, and histamine receptors. However, the mechanism of their antidepressant effects is not clear because the therapeutic effects usually take weeks to develop and may reflect compensatory changes in the central nervous system. Antidepressants, Tricyclic,Tricyclic Antidepressant,Tricyclic Antidepressant Drug,Tricyclic Antidepressive Agent,Tricyclic Antidepressive Agents,Antidepressant Drugs, Tricyclic,Agent, Tricyclic Antidepressive,Agents, Tricyclic Antidepressive,Antidepressant Drug, Tricyclic,Antidepressant, Tricyclic,Antidepressive Agent, Tricyclic,Drug, Tricyclic Antidepressant,Drugs, Tricyclic Antidepressant,Tricyclic Antidepressant Drugs,Tricyclic Antidepressants

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