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PubMed1979

beta-Endorphin: analgesic and hormonal effects in humans.

The pharmacokinetics and the hormonal, analgesic, and behavioral effects of several doses of human beta-endorphin were evaluated after intravenous administration to three patients and intracerebroventricular administration to one patient with pain caused by cancer. These effects were compared to the hormonal effects of intravenously administered morphine sulfate in two patients and an enkephalin analog in two baboons. The mean terminal half-life after intravenous administration of 5 or 10 mg of human beta-endorphin to three patients was 37 min; the mean volume of distribution was 178 ml/kg, and the metabolic clearance rate was 3.2 (ml/min)/kg. The half-life of beta-endorphin in cerebrospinal fluid after intracerebroventricular administration was 93 min, and the volume of distribution was 0.74 ml/kg. A rapid rise in plasma prolactin followed both intravenous and intracerebroventricular beta-endorphin. Intravenous administration did not affect plasma growth hormone, but intracerebroventricular administration suppressed plasma growth hormone. No significant change in plasma growth hormone was noted after intravenous administration of morphine to humans, but plasma growth hormone decreased in one baboon after administration of the enkephalin analog. beta-Endorphin-stimulated release of prolactin occurred at doses lower than those required to produce analgesic and other behavioral effects. When both hormonal and analgesic effects were observed (after 7.5 mg were given intracerebroventricularly), the onset of the hormonal response slightly preceded the analgesic and behavioral responses. These studies suggest that the hormonal effects of beta-endorphin are species dependent and are similar to those of morphine. Hormonal and analgesic effects of beta-endorphin appear to result from the activation of opiate receptors that differ in their locations and characteristics.

Adult↗
PubMedDate not supplied

Analgesic nephropathy in rodents.

While it is clear that humans suffer from "classic" analgesic nephropathy, the causative agents and mechanisms are still not known. A review of the literature revealed that chronic acetaminophen exposure does not produce renal papillary necrosis in rodents or humans. In contrast, while chronic aspirin exposure to rodents results in renal papillary necrosis with renal morphological and functional changes similar to that described in humans, epidemiological studies do not implicate aspirin alone in human analgesic nephropathy. The difference in the effects of aspirin in humans and rats may be due to the inability of epidemiological studies to detect aspirin-induced analgesic nephropathy or more likely to the fact that species differences exist, with the rat being more sensitive than humans. With respect to combinations of aspirin and acetaminophen, with or without caffeine, there are minimal tightly controlled studies. In addition, there is little evidence of enhanced renal papillary necrosis in rodents treated with aspirin and acetaminophen combinations. In summary, it remains to be determined what chemical entities cause "classic" analgesic nephropathy in humans and the mechanisms of this toxicity such that preventative measures can be instituted. Elucidation of the mechanisms of analgesic nephropathy has been hampered due to the lack of animal models that closely mimic the human disease. Rodents do not appear to be an appropriate model.

Acetaminophen↗
PubMed2001

The effect of montage on the analgesic response to percutaneous neuromodulation therapy.

The analgesic response to percutaneous neuromodulation therapy (PNT) is influenced by the location, frequency, and duration of electrical stimulation. We evaluated the effect of different patterns of stimulation (montages) on the acute analgesic response to PNT when applied at the same dermatomal levels in 72 consenting patients with low back pain. All of the patients received a standardized montage (I) and three alternative montage (II-IV) patterns according to a randomized, single-blinded, crossover study design. All of the PNT treatments were administered at identical alternating stimulation frequencies of 15 and 30 Hz for a period of 30 min, three times per week for two consecutive weeks, with 1 wk "off" between each modality. Pretreatment assessments included the health status survey short form (SF-36) questionnaire, as well as visual analog scale scores for pain, physical activity, and quality of sleep (with 0 = the best to 10 = the worst). The pain visual analog scale was repeated 5--10 min after each treatment session. The daily oral analgesic usage was recorded in a patient diary. All four montages produced significant improvements in pain (42%--64%), physical activity (35%--51%), and quality of sleep (28%--46%), as well as 23% to 47% reductions in the daily oral analgesic usage. However, Montage II was significantly more effective than the standard (Montage I) and the other two montages studied. These data suggest that the pattern of stimulation (i.e., montage) can influence the acute analgesic response to PNT.

Adult↗
PubMed1994

Hemodynamic and analgesic profile after intrathecal clonidine in humans. A dose-response study.

BACKGROUND: Epidural clonidine produces effective postoperative analgesia in humans. Observed side effects include hypotension, bradycardia, sedation, and dryness of the mouth. A recent clinical study demonstrated that 150 micrograms intrathecal clonidine administered postoperatively as the sole analgesic agent was effective but produced hypotension and sedation. Animal studies have provided evidence of a biphasic effect on blood pressure after intrathecal clonidine administration, but no data concerning this effect in humans currently exist. This study was performed to evaluate the dose-response hemodynamic and analgesic profiles of intrathecal clonidine administered after a standard surgical intervention, without perioperative administration of additional analgesics, local anesthetics, or tranquilizers. METHODS: In a randomized prospective double-blind study, 30 women who underwent elective cesarean section during general anesthesia with thiopental, nitrous oxide, and halothane were studied. Forty-five minutes after tracheal extubation, a lumbar intrathecal puncture was performed, and the patients received 150 (group 1), 300 (group 2), or 450 (group 3) micrograms clonidine. Postoperative analgesia was assessed on a visual analog scale at rest and after deep cough at standard time points up to 24 h. At the same time points, blood pressure, heart rate, sedation, and respiratory rate also were recorded. RESULTS: Intrathecal clonidine decreased pain in all three groups both at rest and with coughing very shortly after injection, in a dose-dependent fashion. Clonidine 450 and 300 micrograms reduced pain scores significantly earlier (3rd and 6th min after intrathecal injection respectively), compared with 150 micrograms clonidine. Pain relief, defined as the time to first request for supplemental analgesic by patients, lasted 402 +/- 75 min in group 1, 570 +/- 76 min in group 2, and 864 +/- 80 min in group 3; significant differences among all groups; P < 0.01-0.001). Clonidine reduced mean arterial pressure compared with baseline only in group 1 (21 +/- 13%, P < 0.05). Delayed hypotension or bradycardia were not encountered after any of the three dose studies. Sedation was evident in all groups, but group 3 patients were significantly more sedated than group 1 and 2 patients. Respiratory rate and motor activity of the lower extremities were unaffected in all three groups (differences not significant). CONCLUSIONS: These results demonstrate dose-dependent analgesia after intrathecal clonidine at doses as great as 450 micrograms. The nearly immediate analgesic effect observed after intrathecal injection of 300 and 450 micrograms clonidine strongly argues for a spinal rather than a systemic site of action of this alpha 2-adrenergic agonist. After 300 and 450 micrograms intrathecal clonidine a relative hemodynamic stability is observed, suggesting a pressor effect at peripheral sites.

Adult↗
PubMed2001

Magnesium sulfate does not reduce postoperative analgesic requirements.

BACKGROUND: Because magnesium blocks the N-methyl-D-aspartate receptor and its associated ion channels, it can prevent central sensitization caused by peripheral nociceptive stimulation. However, transport of magnesium from blood to cerebrospinal fluid (CSF) across the blood-brain barrier is limited in normal humans. The current study was designed to evaluate whether perioperative intravenous magnesium sulfate infusion affects postoperative pain. METHODS: Sixty patients undergoing abdominal hysterectomy received 50 mg/kg intravenous magnesium sulfate as a bolus dose followed by a continuous infusion of 15 mg x kg(-1) x h(-1) for 6 h (magnesium group) or the same volume of isotonic saline (control group). At the end of surgery, serum and CSF magnesium concentration were measured in both groups. The cumulative postoperative analgesic consumption was measured to assess the analgesic effect using a patient-controlled epidural analgesia device. Pain intensities at rest and during forced expiration were evaluated at 6, 24, 48, and 72 h postoperatively. RESULTS: At the end of surgery, patients in the magnesium group had significantly greater postoperative serum magnesium concentrations compared with both preoperative and control group values (P < 0.001). Despite significantly higher serum magnesium concentrations in the magnesium group, there was no significant difference in magnesium concentration measured in postoperative CSF. Cumulative postoperative analgesic doses were similar in both groups. However, there was observed an inverse relation between cumulative postoperative analgesic consumption and the CSF magnesium concentration in both groups. Visual analog pain scores at rest and during forced expiration were similar and less than 4 in both groups. CONCLUSIONS: Perioperative intravenous administration of magnesium sulfate did not increase CSF magnesium concentration and had no effects on postoperative pain. However, an inverse relation between cumulative postoperative analgesic consumption and the CSF magnesium concentration was observed. These results suggest that perioperative intravenous magnesium infusion may not be useful for preventing postoperative pain.

Adult↗
PubMed2002

Clonidine--a potent analgesic adjuvant.

PURPOSE OF REVIEW: The alpha(2)-adrenoceptor agonist clonidine is one of the most widely investigated substances in anaesthesia and pain therapy. Recently, numerous experimental and clinical studies have allowed a better understanding of its underlying mechanisms of action and interactions with other analgesic drugs. RECENT FINDINGS: Several experimental studies have shown that clonidine may improve the analgesic effect of anti-inflammatory agents and also have significant peripheral antinociceptive effects. Volunteer and clinical studies have demonstrated analgesic effects of clonidine after systemic administration, whereas local administration of plain clonidine (e.g. intra-articular, intravenous regional) showed only limited clinical efficacy. The major clinical place of clonidine may thus be as an adjuvant to other analgesics, as shown in a number of studies in which clonidine has been investigated in combination with local anaesthetics, opioids and ketamine. An increasing number of studies have now investigated clonidine in paediatric patients and have demonstrated that the effects are generally similar to those in adults. Furthermore, it seems that in paediatric patients the side-effects of clonidine are predictable and of limited clinical importance. SUMMARY: During the past decade clonidine has been investigated as an adjuvant for general and regional anaesthesia and in the postoperative period. There is no doubt that clonidine improves analgesia after systemic, spinal or peripheral opioids, and prolongs the analgesic action of most local anaesthetics. The side-effects of usual doses of clonidine are predictable. Given the clinical experience of an increasing number of hospitals, clonidine should no longer be considered an experimental drug, but a useful addendum to the pharmacological armamentarium.

Journal Article↗
PubMed2003

Pro-algesic versus analgesic actions of immune cells.

PURPOSE OF REVIEW: When tissue is destroyed, pain arises. Tissue destruction is associated with an inflammatory reaction. This leads to activation of nociceptors. The following review will concentrate on pro-algesic and analgesic mediators, which arise from immune cells or resident cells in the periphery or the circulation during inflammation. RECENT FINDINGS: In early inflammation endogenous hyperalgesic mediators are produced, including cytokines, chemokines, nerve growth factor as well as bradykinin, prostaglandins and ATP. Simultaneously, analgesic mediators are secreted: opioid peptides, somatostatin, endocannabinoids and certain cytokines. Inflammation increases the expression of peripheral opioid receptors on sensory nerve terminals and enhances their signal transduction, as well as the amount of opioid peptides in infiltrating immune cells. Interference with the recruitment of opioid-containing immune cells into inflamed tissue by blockade of adhesion molecules or by intrathecal morphine injection reduces endogenous analgesia. SUMMARY: Inflammatory pain is the result of the interplay between pro-algesic and analgesic mediators. To avoid central side effects, future analgesic therapy should be targeted at either selectively blocking novel pro-algesic mediators or at enhancing endogenous peripheral analgesic effects.

Journal Article↗
PubMed2004

Morphine metabolites as novel analgesic drugs?

PURPOSE OF REVIEW: Morphine metabolites have attracted continuing interest for their contribution to the desired and unwanted effects of morphine. Among the metabolites of morphine, morphine-6-glucuronide has been given most scientific attention. It accounts for 10% of the morphine metabolism, acts as an agonist at mu-opioid receptors and exerts antinociceptive effects. This review summarizes the recent findings on morphine-6-glucuronide and discusses its potential use as an analgesic. RECENT FINDINGS: Morphine-6-glucuronide has a very long delay between the time course of its plasma concentrations and the time course of its central nervous effects, with 6-8 h probably the longest transfer half-life between plasma and effect site of all opioids administered in humans. This complicates the control of morphine-6-glucuronide therapy when used as an intravenous analgesic, and the long duration of action confers no advantage over other opioids because long-lasting opioid analgesia can be readily obtained with sustained release formulations of other opioids. During acute treatment, however, morphine-6-glucuronide appears to be sufficiently potent to exert peripheral analgesic effects, without exerting major central nervous opioid side effects for a short period of time. The side effects profile does not clearly separate morphine-6-glucuronide from morphine, with reports of similar side effects. There are contrasting reports, however, about similar or less respiratory depression and other side effects compared with morphine after systemic injection. SUMMARY: Morphine-6-glucuronide might qualify as an analgesic but it has several pharmacological properties that make it far from ideal for therapeutic use. Whether it will be a useful addition to the currently established analgesics has yet to be demonstrated.

Journal Article↗
PubMedDate not supplied

Analgesic effects and pharmacokinetics of a low dose of ketamine preoperatively administered epidurally or intravenously.

OBJECTIVES: The aim of this study was to compare the analgesic effects and pharmacokinetics of epidural versus intravenous administration of low doses of ketamine. METHODS: 45 patients scheduled for selective gastrectomy were randomly assigned into 3 groups: 0.5mg/kg ketamine administered epidurally (Kepi group), 0.5 mg/kg ketamine administered intravenously (Kiv group), or 10ml normal saline administered epidurally (Ctr group). Analgesic effects were evaluated using Visual Analog Scale (VAS) pain scores at rest, time to first request for analgesic (TFA), and subsequent morphine consumption. The plasma concentration of ketamine was measured with high performance liquid chromatography (HPLC) in the Kepi and Kiv groups. The elimination half-life of ketamine was calculated. RESULTS: Patients in the Kepi group had significantly lower VAS pain scores, longer TFA, and lower morphine consumption than patients in the Kiv or Ctr groups. Compared with intravenous administration, epidural administration of ketamine resulted in higher plasma concentrations from 90 minutes to 48 hours after injection, and much longer elimination half-life of ketamine, but a lower maximum plasma concentration of ketamine. CONCLUSION: The results suggest that epidural administration of a low dose of ketamine provides more effective analgesic effects as seen post-operatively than intravenous administration. The prolonged half-life and high plasma sustained concentration of epidural ketamine might account for the difference in analgesic effects.

Adult↗
PubMed2006

Efficacy and safety of over-the-counter analgesics in the treatment of common cold and flu.

RATIONALE: Common cold and flu are the most common human illnesses, and over-the-counter (OTC) analgesics are widely used to treat the pain and fever symptoms. Despite the every day use of these analgesic there is little information available in the literature on the efficacy and safety of these medicines in treating colds and flu symptoms. The aim of this review was to determine the safety and efficacy of the analgesics, aspirin, paracetamol and aspirin for the treatment of colds and flu. METHODS: Electronic databases and a personal database were searched and the information retrieved together with information from relevant textbooks has been integrated in the review. RESULTS: The literature search established that there is relatively little information on the use of analgesics in treating colds and flu and that much of the safety and efficacy data must be related to other pain and fever models. The review establishes that aspirin, paracetamol and ibuprofen are safe in OTC doses and that there is no evidence for any difference between the medicines as regards efficacy and safety for treatment of colds and flu (except in certain cases such as the use of aspirin in feverish children). There is also no evidence that these medicines prolong the course of colds and flu by any effect on the immune system or by reducing fever. CONCLUSION: Despite the lack of clinical data on the safety and efficacy of analgesics for the treatment of colds and flu symptoms a case can be made that these medicines are safe and effective for treatment of these common illnesses.

Acetaminophen↗
PubMed2004

Comparison of the analgesic effects of xylazine in sheep via three different administration routes.

OBJECTIVE: To examine the influence of administration route on the analgesic effects of identical doses of xylazine in sheep. A prospective, linear, randomised laboratory study. PROCEDURE: The analgesic response to the administration of 2.5 mg of the alpha2 agonist xylazine either intravenously, intramuscularly or subcutaneously was assessed using an analgesia testing method based upon a learned response to a painful electrical stimulus. RESULTS: Intravenous administration achieved the most rapid onset and highest peak analgesic values of all administration methods, but was characterised by a shorter duration of action (25 min). Intramuscular and subcutaneous administration resulted in a longer duration of action (40 min) and a greater total analgesic response. CONCLUSION: For the routine management of acute pain, intramuscular administration provided the best combination of onset, duration and total analgesic response of the routes examined. The absence of adverse side effects, such as sedation, normally associated with the administration of alpha2 agonists should also encourage the use of this method as a simple and effective means of providing significant analgesia in the sheep.

Adrenergic alpha-Agonists↗
PubMed1993

Characterization of the analgesic effect of paracetamol and caffeine combinations in the pain-induced functional impairment model in the rat.

The analgesic activities of paracetamol (100, 178, 316 and 562 mg kg-1), caffeine (10, 18, 32 and 56 mg kg-1) and combinations of these doses were tested on a pain-induced functional impairment model in the rat. Dysfunction of the right hind limb was induced by an intra-articular injection of 30% uric acid in the knee. Drugs were given orally and the recovery of functionality over time was considered as an expression of analgesia. Paracetamol alone induced a dose-dependent analgesic effect whereas caffeine alone did not show any activity at the assayed doses. Combinations of 316 mg kg-1 paracetamol with either 10, 18, 32 or 56 mg kg-1 caffeine yielded analgesic effects significantly greater than that of paracetamol alone. The highest potentiation was observed with a paracetamol-caffeine mixture of 316-32 mg kg-1. Caffeine coadministration, however, did not significantly change paracetamol plasma levels. No potentiation was obtained with other combinations. Paracetamol plasma levels and analgesic effect observed with administration of 316 mg kg-1 paracetamol alone or 316-32 mg kg-1 of paracetamol-caffeine were fitted to the sigmoidal Emax model according to the Hill equation. The curves obtained were parallel, but that of the combination was shifted to the left. It is concluded that caffeine is able to potentiate the analgesic effect of paracetamol by a pharmacodynamic mechanism, but this only occurs at certain dose combinations.

Acetaminophen↗
PubMed1985

Baclofen as an analgesic in chronic peripheral nerve disease.

Baclofen has shown analgesic properties in a number of animal studies but has failed as a conventional analgesic in the human postoperative dental pain model. In order to test baclofen's analgesic properties in more chronic pain conditions, we selected postherpetic neuralgia and diabetic neuropathy pain as possible trial diseases for baclofen analgesia. 15 patients with postherpetic neuralgia and 10 with diabetic neuropathy pain were treated with baclofen. In the spinal postherpetic neuralgia group and diabetic neuropathy group, there was little evidence of analgesic effect. 6 of 7 patients with facial postherpetic neuralgia had a good response to baclofen during the 3-week trial. Baclofen does not appear to be a conventional analgesic.

Adult↗
PubMed1984

Impairments in analgesic, hypothermic, and glucoprivic stress responses following neonatal monosodium glutamate.

Neonatal administration of monosodium glutamate (MSG) produces in rats neurotoxic degeneration of the circumventricular system, including the medial-basal hypothalamus, depleting several neuropeptides and neurotransmitters in this area. In addition, a number of behavioral and neuroendocrine responses are impaired, including a significant decrease in the analgesic response to cold-water swims (CWS). The present study examined whether the alterations in the analgesic responses following CWS and 2-deoxy-D-glucose (2-DG) induced by neonatal MSG treatment were due either to direct alterations in a pain-inhibitory system, or alternatively, to alterations in a system that processes the stressful consequences or properties of a stimulus. To accomplish this, the analgesic, hypothermic, and locomotor responses following CWS and the analgesic, hyperphagic, and locomotor responses following 2-DG were assessed in rats treated neonatally (days 2, 4, 6, 8, and 10) with either MSG or a vehicle solution. MSG-treated rats displayed significant reductions in both their analgesic and hypothermic responses following CWS, suggesting that MSG treatment impairs an animal's ability to process sufficiently the stimulus properties of the swim as stressful. While MSG treatment potentiated 2-DG analgesia, it reduced 2-DG hyperphagia, suggesting that MSG treatment also impairs coping responses to glucoprivation. These data indicate the importance of the circumventricular system in the coding of stimuli as potential stressors and in the subsequent activation of requisite systems necessary to provide a sustained, coordinated, and synchronous coping response.

Animals↗
PubMed2003

The effects of preoperative inflammation on the analgesic efficacy of intraarticular piroxicam for outpatient knee arthroscopy.

UNLABELLED: We conducted a double-blinded study in 90 patients undergoing elective arthroscopic knee surgery to determine whether there is a role of inflammation in the analgesic efficacy of intraarticular piroxicam. Standardized general anesthetic techniques were used for all patients. At the end of the operation, after harvesting synovial biopsies, patients were randomized into three intraarticular groups equally. Group 1 received 25 mL saline, Group 2 received 25 mL 0.25% bupivacaine, and Group 3 received 25 mL 0.25% bupivacaine and piroxicam 20 mg. After microscopic examination of the synovial materials, the patients were divided into two subgroups, inflammation positive (I+) and inflammation negative (I-). Preoperatively and postoperatively at 1, 2, 4, and 6 h, pain levels, analgesic duration, and postoperative analgesic consumption were recorded. Analgesic duration was significantly longer in the I+ subgroup than the I- subgroup of Group 3 (P < 0.05). Pain scores at 1, 2, and 4 h postoperatively were significantly lower in the I+ subgroup than the I- subgroup of Group 3 (P < 0.05), whereas there were no significant differences among the subgroups of Group 1 and 2. We concluded that preoperative inflammation is one of the most important determinants of analgesic efficacy of intraarticular piroxicam. IMPLICATIONS: Intraarticular administration of piroxicam along with bupivacaine improves postoperative analgesia in synovial inflammation before surgery.

Adult↗
PubMed2003

The antiinflammatory and analgesic effects of baicalin in carrageenan-evoked thermal hyperalgesia.

UNLABELLED: We tested baicalin for its antiinflammatory and analgesic effects (and the mechanisms) in a rat model of carrageenan-evoked thermal hyperalgesia. Pre- or posttreatment with baicalin (10, 30, or 100 mg/kg intraperitoneally) caused a significant analgesic effect with a similar effect of dose-matched ibuprofen. Furthermore, baicalin dose-dependently attenuated tumor necrosis factor-alpha (from 3510 +/- 150 pg/mL to 2860 +/- 148 pg/mL to 1480 +/- 210 pg/mL), interleukin (IL)-1beta (from 3210 +/- 210 pg/mL to 2200 +/- 140 pg/mL to 750 +/- 95 pg/mL), and IL-6 (from 58.5 +/- 9.8 pg/mL to 38.5 +/- 9.0 to 21.0 +/- 8.1 ng/mL) formation but enhanced IL-10 (from 18.1 +/- 2.5 pg/mL to 36.1 +/- 5.5 pg/mL to 71.2 +/- 9.5 pg/mL) production in paw exudates at 4 h after carrageenan injection. Prostaglandin E(2) (PGE(2)) and nitrate formation in the carrageenan-injected paws were dose-dependently inhibited by baicalin (10-100 mg/kg intraperitoneally) (PGE(2): from 15.9 +/- 2.1 ng/mL to 12.1 +/- 1.6 ng/mL to 6.2 +/- 1.8 ng/mL; nitrate: from 39.8 +/- 4.8 microM to 27.5 +/- 3.0 microM to 17.2 +/- 1.6 microM) at 4 h but not at 1.5 h after carrageenan injection. Increased myeloperoxidase activity in carrageenan-injected paws was also dose-dependently reduced by baicalin. These findings suggest that the antiinflammatory and analgesic mechanisms of baicalin may be associated with the inhibition of critical inflammatory mediators, including nitric oxide, PGE(2), and proinflammatory cytokines, accompanied by an increase in IL-10 production, as well as neutrophil infiltration at sites of inflammation. IMPLICATIONS: Our results showed that baicalin possesses an analgesic effect in carrageenan-evoked thermal hyperalgesia. The possible mechanisms of action of baicalin may be associated with the inhibition of proinflammatory mediator overproduction, including cytokines, nitric oxide, and prostaglandin E(2), as well as neutrophil infiltration. This implies that baicalin may be a potential therapeutic analgesic for inflammatory pain.

Animals↗
PubMed1997

Relationship between pharmacokinetics and the analgesic effect of indomethacin in the rat.

The relationship between the pharmacokinetic properties and the analgesic effect of indomethacin (IDM) was evaluated on a carrageenin-induced inflammation model in the rat. Rats were administered the drug in one of two ways: intravenous (i.v.) IDM bolus or i.v. IDM infusion. The analgesic activity was measured by Randall-Selitto test. No correlation was observed between the analgesic effect and the plasma IDM concentration after i.v. bolus administration of IDM. However, in the case of infusion, IDM produced a dose-dependent analgesic effect. In this paper, we demonstrated that the plasma concentration of IDM maintained by i.v. infusion had a prolonged analgesic effect on the carrageenin-induced inflammation model.

Animals↗
PubMed1985

Pharmacological studies of furo [3,2-b]indole derivatives. II. Analgesic effect of FI-302, N-(3-piperidinopropyl)-4-methyl-6-trifluoromethyl-furo[3,2-b]ind ole-2-carboxamide, in experimental animals.

FI-302, N-(3-piperidinopropyl)-4-methyl-6-trifluoromethyl-furo[3,2-b]indol e-2-carboxamide, is a new non-steroidal anti-inflammatory compound. The analgesic effect of FI-302 was investigated in comparison with those of non-steroidal anti-inflammatory drugs (NSAIDs). In the tail pressure, hot plate and D'Amour and Smith methods, FI-302 showed a potent analgesic effect, its efficacy being about 2 to 7 times greater than those of aminopyrine, mepirizole and tiaramide. On the other hand, in these methods, aspirin, ibuprofen and phenylbutazone had little or no effect. FI-302 showed a potent inhibitory effect on the vocalization response produced by electrical stimulation. Moreover, the analgesic effect of FI-302 after intracerebroventricular injection was about 58 to 278 times more potent than those of tiaramide and ibuprofen, and about 1/6 that of morphine. However, the analgesic effect of FI-302 was not antagonized by levallorphan. From these results, it appears that FI-302 has potent analgesic effects which may be produced by both peripheral and central mechanisms, but it is a non-narcotic compound. Consequently, FI-302 should be suitably applicable for clinical purposes.

Animals↗