Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The centrally acting muscle relaxant cyclobenzaprine was thought to be an alpha 2-adrenoceptor agonist that reduced muscle tone by decreasing the activity of descending noradrenergic neurons. In the present study, we examined the effects of cyclobenzaprine on descending neurons by measuring the monosynaptic reflex in rats. Cyclobenzaprine reduced the monosynaptic reflex amplitude dose dependently and this effect was not inhibited by the alpha 2-adrenoceptor antagonists idazoxan and yohimbine. Cyclobenzaprine-induced monosynaptic reflex depression was not attenuated by noradrenergic neuronal lesions produced by 6-hydroxydopamine. However, cyclobenzaprine inhibited monosynaptic reflex facilitation induced by (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane, a 5-HT2 receptor agonist, in spinalized rats markedly, and 5-HT depletion by DL-p-chlorophenylalanine inhibited the depressive effect of cyclobenzaprine on the monosynaptic reflex. These results suggest that cyclobenzaprine is a 5-HT2 receptor antagonist and that its muscle relaxant effect is due to inhibition of serotonergic, not noradrenergic, descending systems in the spinal cord.
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PMID:Cyclobenzaprine, a centrally acting muscle relaxant, acts on descending serotonergic systems. 888 33

Many pains are controlled by non-addictive procedures ranging from exercise to a variety of analgesic medications. Some pains are controlled by analgesic drugs, but at the cost of intolerable side effects. This is true both for non-steroidal anti-inflammatory drugs and opioids. The worst pains are most often controlled by opioids, but problems of tolerance and addiction limit these successes. This contribution provides a statement on non-addictive, non-opioid drugs which help to control pain. Just as these vary in their success, so they vary also in the strength of the scientific evidence which supports their use. The groups of drugs to be considered can be evaluated in three respects; evidence of analgesic effect in controlled trials; evidence of side-effects compared with control substances and with standard experience; evidence of usefulness in clinical practice. The latter which is the most important for practice often has the least scientific proof. Six main classes of drugs are recognized which provide analgesic effects, other than opioids. 1) Non-steroidal anti-inflammatory drugs are widely accepted as analgesics on the basis of animal studies, numerous controlled investigations and clinical practice. Acetaminophene may not be anti-inflammatory, but is recognized as an effective analgesic which in many other respects resembles the above. 2) Muscle relaxants, e.g. cyclobenzaprine or baclofen have varied actions, but often provide some relief of pain. 3) Antidepressants may be analgesic if they relieve depression which is giving rise to pain. This applies to all anti-depressants. Some antidepressants have been shown to be analgesic in the absence of depression. The best accredited of these is amitriptyline. Antidepressants too have significant side effects. A serotoninergic hypothesis is insufficient to explain the actions of antidepressants in relieving pain in the absence of depression. 4) Phenothiazine neuroleptics (and possibly some others) may be analgesic. Drugs reported to be analgesic include chlorpromazine, fluphenazine, perphenazine, trifluoperazine, methotrimeprazine (levomepromazine) among others. Haloperidol has also been utilized. Well controlled evidence exists with the use of methotrimeprazine (levomepromazine) used as an injection. The analgesic effect of oral neuroleptics is less well established and mostly depends upon clinical observation, withdrawal and re-challenge. 5) Anticonvulsants. 6) Other drugs. Non-steroidal anti-inflammatory drugs and some muscle relaxants, e.g. cyclobenzaprine are best used in the short term. The gastrointestinal side effects of non-steroidal anti-inflammatory drugs have been quite troublesome and over 2% of patients followed over five years are at risk of developing peptic ulceration from such medication. Cyclobenzaprine is best used in short term treatment, but may be used intermittently for chronic pain. Antidepressants, neuroleptics, anticonvulsants and some other drugs can be used long term. Topical analgesic agents may also be used.
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PMID:Pharmacological approaches other than opioids in chronic non-cancer pain management. 906 Nov 5

The centrally acting muscle relaxant cyclobenzaprine decreases the amplitude of monosynaptic reflex potentials by inhibiting the facilitatory descending serotonergic influences in the spinal cord. Interestingly, the structure of cyclobenzaprine is much similar to those of amitriptyline and cyproheptadine. In the present study, we attempted to elucidate the relationship between 5-HT(2) receptor antagonistic and inhibitory effects of cyclobenzaprine, amitriptyline, cyproheptadine and ketanserin on the spinal reflexes. Cyclobenzaprine, amitriptyline, cyproheptadine, and ketanserin significantly inhibited facilitatory effects of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on flexor reflexes and mono- and polysynaptic spinal reflex potentials in spinalized rats. In intact rats, these drugs significantly reduced the mono- and polysynaptic reflex potentials. 5-HT depletion significantly prevented the depression of the spinal reflex potentials induced by these drugs. These results suggest that the inhibitory effects of cyclobenzaprine, amitriptyline, and cyproheptadine on mono- and polysynaptic reflex potentials are due to the inhibition of descending serotonergic systems through 5-HT(2) receptors in the spinal cord.
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PMID:Tricyclic analogs cyclobenzaprine, amitriptyline and cyproheptadine inhibit the spinal reflex transmission through 5-HT(2) receptors. 1249 11