Spinal cord norepinephrine action

Zhang C, Davies MF, Guo TZ, Maze M (1999) The analgesic action of nitrous oxide is dependent on the release of norepinephrine in the dorsal horn of the spinal cord. Anesthesiology 91,1401-1407... 

Cardiovascular effect. [6]-shogaol, administered intravenously to rats at a dose of 0.5 mg/kg, produced a rapid fall in blood pressure, bradycardia, and apnea. There was a marked pressure pressor response in blood pressure that occurred after the rapid fall. A dose of 3.6 pM produced inotropic and chronotropic actions on isolated atria in rats. The effect disappeared by repeated injections or pretreatment of 100 mg/kg administered subcutaneously ° k Intravenous doses of 0.1 to 0.5 pg produced a pressor response in a dose dependent manner. The response was markedly reduced by spinal destruction at the sacral cord level. Norepinephrine (10 pg/kg, intravenously) induced pressor response that was not affected by spinal destruction. In rats in which the spinal cord was destroyed at the thoracic cord level, [6]-shogaol-induced pressor response was reduced by hexamethonium (10 mg/kg, intravenously) and phentolamine (10 mg/ kg, intravenously). When the spinal cord was destroyed at the sacral level, the pressor response was not affected by these blockades. In the hindquarters of rats that were perfused with rat s blood, [6]-shogaol produced two pressor responses on the perfusion pressure. The first was accompanied by a rise in systemic blood pressure, was re-... 

Tramadol has about one tenth the pain-relieving ability of morphine.53 There are two enantiomers, and both contribute to pain relief, but via different mechanisms. (+)-Tramadol and the metabolite (+)-0-desmethy 1-tramadol, which is referred to as Ml, are agonists of the mu opioid receptor. (+)-Tramadol inhibits serotonin reuptake and (-)-tramadol inhibits norepinephrine re uptake.25 This latter action enhances the inhibitory effects on pain transmission in the spinal cord. Because the actions of the two enantiomers are complementary, they are usually supplied as a racemic mixture. However, because it is a serotonin-reuptake blocker, interaction with other medications can lead to the occurrence of serotonin syndrome.54... 

Amitriptyline is most frequently used, starting with 10 mg at night increasing to 75 mg. Nortriptyline is better tolerated by some patients. Their general action is to inhibit noradrenaline (norepinephrine) re-uptake by nerve terminals and benefit in neuropathic pain may follow enhanced activity in noradrenergic pain inhibitory paths in the spinal cord. 

At a dosage of 5 mg/kg (i.v.), tetrandrine was found to inhibit the pressor action of norepinephrine release induced by electrical stimulation of spinal cord Tn-L2. However, tetrandrine (5 mg/kg, i.a.) did not obviously attenuate the hypertensive responses to norepinephrine (0.51-16.91 pg/kg, i.v.), indicating that the alkaloid did not affect a1-adrenoceptor-mediated vasoconstriction. Tetrandrine (5 mg/kg, i.a.) was found to decrease the pressor responses to norepinephrine (0.05 and 0.17 pg/kg, i.v.) and markedly reduce the dose-dependent hypertensive responses to a selective a2-adrenoceptor agonist (B-HT920, i.v.), suggesting that the alkaloid reduced a2-adrenoceptor-mediated vasoconstriction [321]. 

Methylphenidate is similar to amphetamine and, like amphetamine, stimulates the central nervous system (CNS), which consists of the brain and spinal cord. Stimulant drugs affect mood and alertness, and depress food appetite by increasing levels of several neurotransmitters in the brain. Although the exact therapeutic mode of action of methylphenidate is not known, the drug has been shown to elevate levels of some of these neurotransmitters, primarily dopamine and norepinephrine (noradrenaline). 

Cyclobenzaprine is a central-acting muscle relaxant that is commonly used to treat pain from injury, muscle spasms, and other painful musculoskeletal conditions. It is structurally related to first-generation tricyclic antidepressants such as imipramine and amitriptyline and appears to inhibit the uptake of norepinephrine in the locus coeruleus. Tricyclic compounds with norepinephrine reuptake-inhibiting properties have been shown to exert analgesic effects in chronic nerve and muscle pain by acting primarily within the central nervous system at brainstem as opposed to spinal cord levels, although their action on the latter may contribute to their overall skeletal muscle relaxant activity. The exact mechanism of action of cyclobenzaprine is unknown. 

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