Evidence of potential analgesic effects of ammoxetine

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Evidence of potential analgesic effects of ammoxetine

Chronic pain is regarded as third most prevalent health problem in the world. Neuropathic pain and fibromyalgia are often treated with the selective serotonin (5-HT) and norepinephrine (NE) reuptake inhibitors (SNRIs). One of the potent SNRI is ammoxetine ((±)-3-(benzo[d] [1,3]dioxol-4-yloxy)-N-methyl-3-(thiophen-2-yl)propan-1-amine) .

Ting-ting Zhang et al conducted a study to assess the  acute analgesic properties of ammoxetine in different animal models. Additionally, the involvement of monoamines in its analgesic actions was studied. The analgesic effects of ammoxetine was assessed in the models of acetic acid- and formalin-induced pain in mice, neuropathic pain induced by sciatic nerve injury (SNI), chronic constriction injury (CCI) and reserpine-induced fibromyalgia pain in rats. High performance liquid chromatography with electrochemical detection (HPLC-ECD) was used to measure the contents of 5-HT and NE in brain regions of fibromyalgia rats. Duloxetine was used as a positive control drug throughout the study for all experiments.

Results indicated that oral administration of ammoxetine (0.625–10 mg/kg) or duloxetine (2.5–40 mg/kg) dose-dependently lowered the number of acetic acid-induced writhing and formalin-induced first phase and second phase paw licking time in mice. Oral administration of ammoxetine (2.5–10 mg/kg) or duloxetine (10 mg/kg) alleviated mechanical allodynia in SNI and CCI rats and thermal hyperalgesia in CCI rats. The oral adminstration of ammoxetine (2.5–10 mg/kg) or duloxetine (10 mg/kg) relieved mechanical allodynia in SNI and CCI rats and thermal hyperalgesia in CCI rats. Pretreatment with para-chlorophenylalanine methyl ester hydrochloride (PCPA, a 5-HT synthesis inhibitor) or α-methyl-para-tyrosine methylester (AMPT, a catecholamine synthesis inhibitor) was employed to terminate the antiallodynic effect of ammoxetine in CCI rats. Oral administration of ammoxetine (30 mg/kg) or duloxetine (50 mg/kg) remarkably attenuated tactile allodynia in rats with reserpine-induced fibromyalgia. Administration of ammoxetine (10, 30 mg/kg) or duloxetine (30, 50 mg/kg) dose-dependently increased the 5-HT and NE levels, and decreased the metabolite ratio of 5-HT (5-HIAA/5-HT) in the spinal cord, hypothalamus, thalamus and prefrontal cortex.

It was thus inferred that ammoxetine alleviates inflammatory, continuous, neuropathic and fibromyalgia-related pain in animal models more effectively, as compared to duloxetine. This can be ascribed to amplified neurotransmission of 5-HT and NE in the descending inhibitory systems.

Source:

Acta Pharmacol Sin.

Link to the source:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5022096/

Original title of article:

Evaluation of the analgesic effects of ammoxetine, a novel potent serotonin and norepinephrine reuptake inhibitor

Authors:

Ting-ting Zhang et al

Acta Pharmacol Sin.
SearchTags: 
Therapeutic, Ammoxetine, Fibromyalgia, Nerves, SNRI, Efficacy
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