Enhancement of central norepinephrine and 5-hydroxytryptamine transmission by tricyclic antidepressants. A comparison. 1979

C Sangdee, and D N Franz

The relative abilities of 1--3 mg/kg of desipramine (DES), imipramine (IMIP), amitriptyline (AMI), and chlorimipramine (CI-IMIP) to enhance synaptic transmission mediated by either NE or 5-HT were determined by testing their effects directly on NE or 5-HT transmission to sympathetic preganglionic neurons in unanesthetized, spinal cats. Effects on NE transmission were assessed on intraspinal excitatory pathways which utilize NE as a transmitter. Effects on 5-HT transmission were assessed on 5-HT-mediated depression of spinal sympathetic reflexes produced by 30 mg/kg of 5-HTP. Both DES and IMIP markedly enhanced transmission through the intraspinal excitatory NE pathways whereas AMI and CI-IMIP depressed transmission. However, both AMI and CI-IMIP modestly enhanced transmission in cats depleted of central 5-HT by pretreatment with parachlorophenylalanine. The relative potencies of the four drugs on excitatory NE transmission were DES greater than IMIP greater than AMI greater than CI-IMIP. Each of the four drugs also enhanced the 5-HTP-induced depression of spinal sympathetic reflexes, but their relative potencies on 5-HT transmission were just the opposite to those found on NE transmission. Therefore, all four drugs enhanced transmission by both NE and 5-HT, but their relative selectivities for the two transmitters differed markedly and were complementary. In general, the results support those of previous studies based on less direct methods for assessing inhibition of amine reuptake by tricyclic antidepressants.

UI MeSH Term Description Entries
D007099 Imipramine The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. Imidobenzyle,Imizin,4,4'-Methylenebis(3-hydroxy-2-naphthoic acid)-3-(10,11-dihydro-5H-dibenzo(b,f)azepin-5-yl)-N,N-dimethyl-1-propanamine (1:2),Imipramine Hydrochloride,Imipramine Monohydrochloride,Imipramine Pamoate,Janimine,Melipramine,Norchlorimipramine,Pryleugan,Tofranil
D008297 Male Males
D009435 Synaptic Transmission The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES. Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
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
D002415 Cats The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801) Felis catus,Felis domesticus,Domestic Cats,Felis domestica,Felis sylvestris catus,Cat,Cat, Domestic,Cats, Domestic,Domestic Cat
D002997 Clomipramine A tricyclic antidepressant similar to IMIPRAMINE that selectively inhibits the uptake of serotonin in the brain. It is readily absorbed from the gastrointestinal tract and demethylated in the liver to form its primary active metabolite, desmethylclomipramine. Chlorimipramine,Anafranil,Chlomipramine,Clomipramine Hydrochloride,Clomipramine Maleate (1:1),Clomipramine Monohydrochloride,Hydiphen,Hydrochloride, Clomipramine,Monohydrochloride, Clomipramine
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
D004558 Electric Stimulation Use of electric potential or currents to elicit biological responses. Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical
D005260 Female Females
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

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