Disease relevance of Fenazoxine

• Nefopam for severe hiccups [1].
• Side effects included mild dizziness and hypothermia after nefopam and mild elevation of diastolic arterial pressure after nefopam and propoxyphene [2].
• The analgesic efficacy and toxicity of oral diclofenac sodium 50 mg (q.i.d.) vs. nefopam 60 mg (q.i.d.) and a combination of 640 mg ASA and 40 mg codeine (q.i.d.) in cancer patients with moderate to severe chronic pain has been evaluated in a randomized double-blind study [3].
• This novel action of nefopam may be of great interest for the treatment of neurodegenerative disorders involving excessive glutamate release and neurotransmission [4].
• Nefopam in postoperative pain [5].

Psychiatry related information on Fenazoxine

• Nefopam displaced 3H-batrachotoxinin and inhibited the uptake of 22Na in the micromolar range and it protected mice against electroshock induced seizures [6].
• She now obtains nefopam by prescription forgery and self-administers intramuscular nefopam 300 mg/d. She experiences anticholinergic effects of nefopam and, when attempting withdrawal, depressive symptoms [7].
• RESULTS: There were 70 reports of adverse reactions thought to be causally related to nefopam, most of which appear to be predictable extensions of the pharmacological effect of nefopam, and included confusion, hallucinations, convulsions, dizziness, headache, sweating, urinary retention, nausea, vomiting, tachycardia and palpitations [8].

High impact information on Fenazoxine

• Relative efficacy, based on summed pain intensity differences, showed measurable but modest dose-dependent analgesia with nefopam, suggesting that the effectiveness of 65 mg propoxyphene lay between 45 mg nefopam and placebo [2].
• Estimated relative potency of nefopam to aspirin was 10.4 with a 95% confidence interval of 6.3 to 20.8 for SPID, indicating that the analgesic potency of nefopam, 60 mg, was equivalent to that of aspirin, 650 mg [9].
• A comparison was made of morphine and nefopam in 74 patients who required parenteral analgesia for moderate to severe postoperative and somatic pain, using a single administration, 2-dose level, double-blind design [10].
• However, when 'higher' dose ratios were compared, morphine and pethidine were usually more effective than nefopam, possibly due to a 'ceiling effect' for analgesia which may occur with higher doses of nefopam, as with other simple analgesics [11].
• RESULTS: The median effective analgesic dose (median value and 95% confidence interval) of nefopam and ketoprofen were, respectively, 28 mg (17-39 mg) and 30 mg (14-46 mg) [12].

Chemical compound and disease context of Fenazoxine

• Sweating and tachycardia were observed more frequently after nefopam, whereas sedative side-effects were more common after pethidine [13].
• However, following clonidine administration the recovery time was prolonged and hypotension was significantly greater than after nefopam [14].
• Ketorolac, ketoprofen and nefopam are often used in the treatment of postoperative pain [15].
• On the other hand, nefopam was effective against NMDA, QA and KA induced clonic seizures in mice [6].
• Effect of a non-opiate analgesic, nefopam hydrochloride, on stress gastric ulcer in rats [16].

Biological context of Fenazoxine

• The authors evaluated the effects of nefopam on the major thermoregulatory responses in humans: sweating, vasoconstriction, and shivering [17].
• However, no information is presently available on the oral kinetics of (+) and (-) nefopam in humans [18].
• For the entire study period (loading dose and PCA), morphine use was less for the nefopam group (34.5 (19.6) vs 42.7 (23.6) mg; P=0.01) [19].
• Following oral administration, (+) and (-) nefopam were rapidly absorbed with bioavailabilities of 44% and 42%, respectively, probably due to a first-pass effect [18].
• Both left ventricular systolic work index and oxygen consumption index were similar in the two groups before extubation, increased after extubation, and further increased in control patients showing a statistical difference compared to patients treated with nefopam [20].

Anatomical context of Fenazoxine

• A single intraperitoneal injection of nefopam was administered twenty minutes prior to the chronic constriction injury of the sciatic nerve (CCI rats) [21].
• A sensitive and selective gas-liquid chromatographic method for the determination of nefopam in human plasma, saliva and cerebrospinal fluid has been developed [22].
• Nefopam excretion in human milk [23].
• Phenylephrine-precontracted rat aortic strips with intact endothelium were relaxed by R- and S-flurbiprofen and nefopam in a concentration-dependent manner [24].
• Adverse effects during therapeutic use and after overdose of nefopam are known to involve the central nervous system (confusion and convulsions), the cardiovascular system (tachycardia and palpitations) and the kidneys (oliguria and renal failure) [25].

Associations of Fenazoxine with other chemical compounds

• Assessment of the analgesic efficacy of nefopam hydrochloride after upper abdominal surgery: a study using patient controlled analgesia [26].
• Compared with the control group (43 [7-92] mg), median [range] cumulative morphine consumption for 24 h after the study started was halved in the nefopam group (21 [3-78] mg, p <0.001) and 20% lower in the propacetamol group (35 [6-84] mg, p = 0.15) [27].
• It is proposed that both the rat and cockroach enzyme may contain, along with the anionic and esteratic sites, an "electron deficient" (ED) binding site which may exhibit selectivity for acephate and nefopam [28].
• Intrathecal injection of codeine, buprenorphine, tilidine, tramadol and nefopam depresses the tail-flick response in rats [29].
• After saline (control) and diazepam, paracetamol absorption was normal but after morphine or nefopam, absorption was delayed markedly, presumably as a result of delayed gastric emptying [30].

Gene context of Fenazoxine

• In vitro binding assays revealed that nefopam possesses moderate affinity for histamine H1 and H2 receptor subtypes, with IC50 of 0.8 and 6.9 microM, respectively, but no affinity for histamine H(3) receptor subtype until 100 microM [31].
• Nefopam (100 microM) effectively prevented NMDA receptor-mediated early appearance (30 min) of toxicity signs induced by the VSSC activator veratridine [4].
• After I.V. administration, the enantiomers of desmethylnefopam exhibited lower concentrations and longer half-lives (20.0 h for DES1 and 25.3 h for DES2) relative to nefopam enantiomers [18].
• Although nefopam also bound to the ED site in cockroach AChE, it did not inhibit the enzyme [32].
• The possible involvement of central serotonergic pathways in the mechanism of action of nefopam was investigated in male albino mice [33].

Analytical, diagnostic and therapeutic context of Fenazoxine

• Analgesia through nefopam (30 mg, 60 mg, 90 mg), aspirin (325 mg, 650 mg), and placebo were compared in 122 hospitalized patients with moderate to severe postoperative, fracture, or other somatic pain [9].
• On each experimental day, four recruitment (intensity-response) curves of the R(III) reflex were constructed: before (control period) and then 30, 60 and 90 min after the intravenous injection of nefopam (20 mg) or a placebo [34].
• Patients receiving nefopam had a mean (+/- s.e.m.) cumulative morphine consumption of 4.1 +/- 0.8 mg in the first hour, compared with 8.5 +/- 0.8 mg in the control group (P less than 0.01) [26].
• Nefopam injected after constriction was ineffective [21].
• Determination of plasma nefopam by liquid chromatography and electrochemical detection [35].

References