Tricyclic antidepressants analgesic activity

Drugs and chemicals are known to cause activated interaction. The depressant action of opioid drugs is enhanced by drugs acting on the central nervous system (CNS) such as alcohol, anesthetics, anxiolytics, hypnotics, tricyclic antidepressants, and antipsychotics. Concomitant administration of opioid analgesics and monoamine oxidase inhibitors (MAOIs) should be avoided, or extra care should be taken if such a therapy is inevitable. Fatal reactions are reported when treated along with selegiline. Interactions also are reported with cyclizine, cimetidine, mexiletine, cisapride, metoclopramide, or domperidone. 

Examples (1) A plethora of drug substances , for instance muscle relaxants, sedatives-hypnotics, tricyclic antidepressants, antipsychotic, antihistaminics, and alcohols are observed to interact with opiate analgesics to augment and accelerate their overlapping pharmacological activities, namely anticholinergic effects and respiratory depression. 

The CNS depressant effects of opioids and the tricyclic antidepressants are expected to be additive. The reasons for the increased morphine levels and analgesic effects that occur with some tricyclics are not understood. The increased analgesia may be due not only to the increased serum levels of morphine, but possibly also to some alteration in the way the morphine affects its receptors. Dextropropoxyphene probably inhibits liver metabolism of some tricyclic antidepressants by inhibiting the activity of the cytochrome P450 isoenzyme CYP2D6, and as a result the serum levels of the tricyclic antidepressants rise. It is suggested that the methadone may possibly inhibit the hydroxylation of the desipramine, thereby raising its levels. ... 

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. 

They are particularly effective for neuropathic pain and their efficacy for post-herpetic neuralgia may be greater than that of the newer pregabalin [2]. Tricyclics are commonly used to treat headaches, fibromyalgia, neck and low back pain. The mechanism of the antinociceptive activity of the tricychc antidepressants is largely unknown, and appears to be distinct from then-antidepressant properties. It may be related to sodium chaimel blockade. Analgesic effects are achieved with lower doses and quicker onset than antidepressant effects. 

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