Human pharmacology and abuse potential of meptazinol.

Meptazinol was assessed in nine opioid abusers according to a double-blind, randomized, crossover design to determine if it produced typical morphine effects. A comparison of physiologic and subjective effects was made between morphine, 7.5, 15, and 30 mg, meptazinol, 70, 140, and 280 mg, and placebo. Both drugs constricted pupils. Meptazinol, 140 and 280 mg, decreased body temperature. Valid relative potency estimates of morphine to meptazinol were obtained for self-reported liking, opiate symptoms, and pupillary constriction. Meptazinol did not increase euphoria or sedation scale scores but did increase dysphoria scale scores. In the therapeutic dose range, meptazinol produced miosis, morphine-like identification and symptoms, limited liking, and some dysphoria. Dysphoria predominated at the 280 mg dose of meptazinol. From these data, it is concluded that meptazinol is not a typical morphine-like drug and has limited abuse potential.

Intramuscular meptazinol and morphine in postoperative pain.

Meptazinol is an agonist-antagonist opioid analgesic believed to be unique in its selectivity for mu1 (high affinity) receptors and its cholinergic activity. Our objectives were to determine the relative analgesic potency of intramuscular meptazinol and morphine and to compare mood and side effects in 102 patients with cancer who have postoperative pain. Meptazinol (50, 100, and 200 mg) and morphine (4, 8, and 16 mg) were given for moderate to severe pain in a double-blind, randomized but balanced, incomplete block design. Serial multiple assessments of pain, relief, mood, and side effects were made. The most precise estimates of relative analgesic potency indicate that meptazinol is equivalent to 10 mg morphine at 120 mg (95% confidence interval 80 to 170 mg) for peak effect and at 175 mg (95% confidence interval 125 to 270 mg) for total effect. Mean (+/- SE) times to peak effect and to remedication were 0.9 +/- 0.1 and 3.6 +/- 0.2 hours for meptazinol and 1.4 +/- 0.1 and 4.8 +/- 0.4 hours for morphine at equianalgesic peak effects. The percentages of subjects with one or more side effects were 18, 49, and 73 for graded meptazinol doses and 32, 49, and 65 for graded morphine doses. Mean numbers of side effects per subject were 0.3, 1.5, and 3.5 for meptazinol and 0.5, 0.7, and 1.7 for morphine. Profiles of side effects differed. Mood improvement and overall satisfaction were dose related and greater for morphine than for meptazinol. Side effects may limit the use of meptazinol in doses that relieve severe postoperative pain.

Meptazinol. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy.

Meptazinol is a new opioid-type analgesic with mixed agonist/antagonist properties. It may be given orally, intravenously or intramuscularly. In studies in patients with moderate to severe pain of various aetiologies, usually following surgery or in obstetrics, the characteristics of analgesia with meptazinol were comparable to those seen with equianalgesic doses of pentazocine, pethidine or a combination of dextropropoxyphene and paracetamol. Preoperative use and use as a component of anaesthesia require further investigation before conclusions may be drawn on its effectiveness in these areas. Onset of action, recorded in a few studies, was faster than that with the other analgesics but duration was shorter than that of morphine, buprenorphine and pentazocine. Only a small number of patients with chronic pain have received long term therapy with meptazinol; in such patients there was no need for increased doses as treatment progressed. Respiratory depression has only been observed in patients receiving meptazinol as a premedication or while undergoing anaesthesia. Similarly any haemodynamic changes have been limited to preoperative patients or patients undergoing anaesthesia. Like other agonist/antagonist analgesic drugs, the abuse potential of meptazinol seems relatively low, but only wider clinical use for longer periods can establish this with certainty. The most commonly reported side effects have been gastrointestinal in nature, and although the incidence of central nervous system side effects has been relatively low, drowsiness and dizziness have caused occasional problems. Thus, meptazinol is a relatively potent but safe addition to the analgesics available for treatment of the patient with moderate to severe pain.

Meptazinol and morphine in postoperative pain assessed with a new method for onset and duration.

Meptazinol, m-(3-ethyl-1-methyl-hexahydro-1-H-azepin-3-yl) phenol hydrochloride is a centrally active opioid analgesic with a specificity for the mu-1 receptor. It has been reported to lack many of the side effects commonly observed with morphine and morphinelike drugs in man. The objective of this study was to assess the analgesic efficacy and safety of meptazinol (50 mg and 100 mg) relative to morphine (5 mg and 10 mg) when administered intramuscularly for the treatment of postoperative pain. In addition, a new clinical method for measuring onset and duration and a statistical technique for evaluating the study data are presented. One hundred and seventeen patients were evaluated for 6 hours in a randomized double blind, single dose, parallel-groups trial. Estimates of relative potency for hourly pain and relief parameters, and the summary variables sum of pain intensity differences (SPID) and total pain relief (TOTPAR) were performed. The estimate of relative potency of meptazinol to morphine for pain relief was 0.19 at 1/2 hour (i.e. 100 mg of meptazinol was approximately equivalent to 20 mg of morphine). Thereafter, there was a rapid decline of efficacy for meptazinol, with a relative potency estimate of 0.12 at 1 hour and 0.06 at 2 hours. The distribution functions for several time related events were estimated including time to onset, duration and time to remedication. The two drugs had approximately equal onset, but meptazinol had significantly shorter duration. More patients on meptazinol required remedication with a rescue analgesic and at an earlier time than patients on morphine.(ABSTRACT TRUNCATED AT 250 WORDS)

A double-blind comparison of ibuprofen, placebo and ibuprofen with meptazinol in soft tissue rheumatism.

The administration of ibuprofen potentiates and prolongs the analgesic effect of meptazinol when the two drugs are given simultaneously to mice. A double-blind three-way crossover study of placebo, ibuprofen (1600 mg/day) and ibuprofen (1600 mg/day) plus meptazinol (400 mg/day) was carried out in 45 patients with soft tissue rheumatism to see if the same potentiation could be demonstrated in man. Treatment order was randomized and each regimen was given for 2 weeks preceded by 1 week on paracetamol alone. Assessments were made, on entry and after each treatment period, of pain parameters using visual analogue or verbal rating scales. Patients' overall impression and final preference showed both active treatments to be better than placebo and demonstrated a slight preference for the combination.

Double-blind parallel study of meptazinol versus diflunisal in the treatment of lumbago.

Seventy out-patients with acute back pain participated in a double-blind comparative trial of the clinical efficacy and tolerance of orally administered meptazinol and diflunisal. Half of the patients received 200 mg meptazinol or 250 mg diflunisal 4-times daily for up to 3 weeks, depending on the duration of pain. Patients were examined 4 times at 1-week intervals for their capability to do daily tasks, for their capacity for forward bending, thoraco-lumbar torsion, straight leg raising, static hip flexion and sit-ups, and for subjective assessment of pain. Side-effects were recorded on a questionnaire. Both treatments produced marked improvement in most of the parameters assessed, often within the first week and, overall, the results were similar with the two drugs. Few side-effects were reported and those that were recorded were slight and similar in incidence apart from nausea in 5 meptazinol-treated patients and smarting and burning on urination in 2 patients receiving diflunisal.

A double-blind comparison of meptazinol versus paracetamol and placebo in acute and chronic painful conditions presented to the general practitioner.

A double-blind study was carried out in 90 patients with acute or chronic painful musculoskeletal conditions of at least moderate severity to compare the effectiveness over a 72-hour period of oral treatment, 3 to 6 hourly, with 200 mg meptazinol, 1 g paracetamol and placebo. Assessments of pain by physicians and patients indicated that both active treatments produced effective analgesia compared with placebo. No significant differences were observed between meptazinol and paracetamol. The frequency of adverse effects reported was low and similar in all three treatment groups.

Double-blind comparison of meptazinol (200 mg) and dextropropoxyphene/paracetamol in a multi-centre, general practice setting.

A multi-centre, double-blind, double-dummy trial was carried out in general practice to compare the effectiveness and tolerance of oral meptazinol with dextropropoxyphene/paracetamol in patients with acute or chronic painful conditions. Patients received doses of 400 mg meptazinol or 65 mg dextropropoxyphene plus 650 mg paracetamol every 3 to 6 hours as required up to a maximum of 4 doses per day over a period of 14 days. No significant difference in analgesic efficacy, as assessed by the patients on a visual analogue pain rating scale, was found between the two treatments. The results are discussed in terms of the benefit/risk ration of polypharmic and single compound drugs.

A comparison between meptazinol and dextropropoxyphene plus paracetamol in elderly patients with musculoskeletal pains.

The efficacy and acceptability of meptazinol and dextropropoxyphene plus paracetamol were compared in 32 elderly patients with various types of musculoskeletal pain. A double-blind crossover technique was used. After at least 1 week in hospital, the previous analgesic treatment was stopped and single-blind placebo was given for 1 day. Patients then received, at random, 5-days' treatment with either 200 mg meptazinol 4-times daily or 65 mg dextropropoxyphene plus 650 mg paracetamol 4-times daily before being crossed over to the alternative medication for a further 5 days. If necessary, up to 4 tablets a day were allowed of 500 mg aspirin plus 50 mg caffeine as a 'rescue' analgesic. Assessments were made before (on placebo) and at the end of each treatment period of pain severity and effect on patients' sleep, and details recorded of 'rescue' analgesic consumption and any side-effects. At the end of the trial, an overall assessment was made of the effectiveness and tolerance of each treatment and patients were asked which they preferred. The results showed that both treatments reduced pain severity significantly for all the parameters measured; however, most patients needed additional pain relief. Few side-effects were reported during either treatment period.

A double-blind comparison of meptazinol versus placebo in chronic rheumatoid arthritis and osteoarthritis.

A double-blind, placebo-controlled, between-patient evaluation of the analgesic properties of oral meptazinol was carried out in 60 patients suffering from chronic pain due to rheumatoid arthritis and osteoarthritis. Patients were allocated, at random, to receive either 200 mg meptazinol every 3 to 6 hours as required or identical matching placebo for a total period of 72 hours. Data from 57 patients (30 on meptazinol, 27 on placebo) were suitable for analysis. Pain intensity in five major categories was assessed using a 4-point verbal rating scale by a clinician before the first dose and at the end of the trial period. Patients performed a self-assessment of pain prior to taking the first dose and subsequently at 2,4,24, 48 and 72 hours using 100 mm visual analogue scales and verbal rating scales. The clinician-rated pain scores showed no significant difference between the two groups in initial pain intensity. After 72-hours' treatment , there was a significant (p less than l.01) reduction in pain intensity after 2 hours which was maintained throughout the trial period. There was no significant reduction in pain intensity inpatients taking placebo. Visual analogue scale scores and pain intensity difference scores showed significantly (p less than 0.01) greater reduction in pain intensity at all time points in the meptazinol- treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

A double-blind comparison of meptazinol and placebo in patients with acute and chronic pain presenting to the general practitioner.

In a double-blind study the analgesic efficacy and acceptability of meptazinol 200 mg was compared with placebo in patients suffering from acute or chronic pain. Patients were randomly allocated to receive either 200 mg of meptazinol or one tablet of placebo 4 to 6 hourly over a 14-day period. Clinical evaluations were made by the physician at baseline and again at the end of the study. The patients made daily recordings of pain using a visual analogue scale. The results showed that meptazinol was a more effective and acceptable analgesic than placebo. There was no significant difference in the incidence of adverse effects reported by patients in either treatment group.

First impressions of the use of meptazinol in general practice.

Meptazinol which is a potent opiate antagonist analgesic has been assessed by the oral route at a dose of 200 mg 3-6 hourly. The analgesic profile shows a significant fall in pain score by 2 hours which was the earliest recording time. Satisfactory pain relief was maintained during 3 days of treatment. The side-effect profile was of a low order and there was no adverse effect on haematological and biochemical screens.

Double blind study of meptazinol versus pentazocine and placebo in postoperative pain treatment.

The purpose of this double blind study was to evaluate the efficiency and safety of a new analgesic drug meptazinol, compared to pentazocine and placebo, in patients suffering from postoperative pain. Subjective and objective parameters were controlled. It appeared clearly that meptazinol had a potent analgesic effect with rapid onset, but rather short duration. Analgesic effect of pentazocine appeared more slowly, but persisted for a longer time. The two active drugs had no effects on the objective parameters measured.

Meserine, a novel carbamate AChE inhibitor, ameliorates scopolamine-induced dementia and alleviates amyloidogenesis of APP/PS1 transgenic mice.

AIMS: To investigate whether Meserine, a novel phenylcarbamate derivative of (-)-meptazinol, possesses beneficial activities against cholinergic deficiency and amyloidogenesis, the two major pathological characteristics of Alzheimer's disease (AD). METHODS: Ellman's assay and Morris water maze were used to detect acetylcholinesterase (AChE) activity and evaluate spatial learning and memory ability, respectively. Both high content screening and Western blotting were carried out to detect ß-amyloid precursor protein (APP), while RT-PCR and ELISA were conducted to detect APP-mRNA and ß-amyloid peptide (Aß). RESULTS: In scopolamine-induced dementia mice, Meserine (1 mg/kg, i.p.) significantly ameliorated spatial learning and memory deficits, which was consistent with its in vitro inhibitory ability against AChE (recombinant human AChE, IC50 = 274 ± 49 nM). Furthermore, Meserine (7.5 mg/kg) injected intraperitoneally once daily for 3 weeks lowered APP level by 28% and Aß42 level by 42% in APP/PS1 transgenic mouse cerebrum. This APP modulation action might be posttranscriptional, as Meserine reduced APP by about 30% in SH-SY5Y-APP695 cells but did not alter APP-mRNA level. And both APP and Aß42 lowering action of Meserine maintained longer than that of rivastigmine. CONCLUSION: Meserine executes dual actions against cholinergic deficiency and amyloidogenesis and provides a promising lead compound for symptomatic and modifying therapy of AD.

Effect of meptazinol on chronic anticoagulant therapy.

Six elderly hospitalized patients (four female, two male; mean age 85.3 years) stabilized on warfarin therapy were treated with meptazinol (200 mg four times daily) for 7 days. There was no significant difference from pretreatment levels either in mean warfarin dosage prothrombin index after introduction or withdrawal of meptazinol. These findings provide no evidence for any major interaction between warfarin and meptazinol.

The use of intramuscular meptazinol in the relief of post-operative pain after abdominal hysterectomy--a review.

In previously published studies of post-abdominal hysterectomy pain control reviewed here, meptazinol in doses of 50, 75 and 100 mg intramuscularly (i.m.) caused significant dose-related pain relief. Meptazinol 100 mg i.m. was equipotent as an analgesic when compared with either Omnopon 20 mg i.m., pentazocine 60 mg i.m. or pethidine 100 mg i.m. Meptazinol in doses of 60, 75 and 100 mg i.m. was not significantly different from pethidine 100 mg in relieving pain when assessed by the pain relief score.