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Multiple doses of paracetamol plus codeine taken immediately after oral surgery.

A double-blind randomized analgesic trial was carried out in 180 patients undergoing surgical removal of an impacted lower wisdom tooth. The patients received the first dose of either paracetamol 1000 mg plus codeine 60 mg, paracetamol 500 mg plus codeine 30 mg or placebo immediately after surgery during the effect of the local anaesthetic. The mean pain intensity, the duration of effect and the number of patients needing additional analgesics were all significantly dose related. In the evaluation procedure a pain intensity index was defined which took into account both the efficacy and the duration of effect. In addition, the analgesic efficacy was calculated over a 12 hour period after first medication and thereby including the efficacy of a second dose, if taken. Paracetamol 1000 mg plus codeine 60 mg followed by paracetamol 500 mg plus codeine 30 mg after around 5 hours was a very effective treatment and over 40% of these patients did not need any further pain relief during the evaluation period. In conclusion, an effective analgesic taken immediately after oral surgery reduces the total pain and diminishes the need of analgesics.

Acetaminophen↗

Double-blind comparison of the analgesic potency of ciramadol, codeine and placebo against postsurgical pain in ambulant patients.

The efficacy and safety of ciramadol (Cir) as an analgesic in relieving moderate to severe pain after oral surgery has been studied in 79 patients randomly assigned to receive single oral doses of Cir 15, 30 or 60 mg, codeine 60 mg or placebo. During the 6-hour observation period, the three ciramadol-treated groups indicated greater pain relief than the codeine 60 mg or placebo groups. In general, Cir 60 mg was significantly more effective than codeine 60 mg, and all doses of Cir were superior to placebo. The proportion of patients in each Cir group reporting adverse experiences was significantly higher than in either the placebo or codeine groups. The experimental system proved very effective in demonstrating analgesic potency of Cir. The very high incidence of side-effects in the three ciramadol-treated groups makes it unfit for further clinical use in ambulant patients.

Adult↗

Quantitative, noninvasive assessment of antidiarrheal actions of codeine using an experimental model of diarrhea in man.

Enteric coating of a capsule has been used to deliver a bolus of radioisotope to the ileocecal region. This has allowed quantitative assessment of regional colonic transit in a group of healthy subjects whose proximal colonic transit was accelerated by lactulose 20 ml thrice daily. In this experimental model of diarrhea, codeine delayed transit from mouth to terminal ileum and also delayed transit through the ascending colon from 5.3 +/- 2.5 hr to 7.4 +/- 2.5 hr, N = 11, P < 0.05. Furthermore, codeine delayed whole colon transit, as assessed by geometric center analysis, which showed the delay to be most marked in the right colon with little effect noted in the left colon. In addition, codeine significantly reduced the number of retrograde movements observed and reduced the colonic response to eating. The antidiarrheal effect of codeine appears to be due to a combination of delayed mouth-cecum transit plus an additional delay in the ascending colon. This colonic delay may be partially explained by a reduction in postprandial propulsive movements that were seen in this model of diarrhea.

Adult↗

Flurbiprofen, aspirin, codeine, and placebo for postpartum uterine pain.

Flurbiprofen (Ansaid, Upjohn), a substituted phenyl propionic acid, is a new analgesic/anti-inflammatory agent. To evaluate its relative efficacy in noninflammatory pain, 159 hospitalized women with moderate or severe postpartum uterine cramps were given single oral doses of 50 mg of flurbiprofen, 650 mg of aspirin, 60 or 120 mg of codeine sulfate, or placebo in a parallel, stratified, randomized block, placebo-controlled, double-blind trial. Patients rated pain intensity, pain relief, and side effects in uniform interviews for six hours after treatment. All measures of peak and summed analgesia exhibited significant differences among the five treatments. Flurbiprofen and aspirin showed the greatest analgesic response and were significantly superior to placebo. Results of codeine treatment were equivocal with no evidence of a positive dose response. Side effects were unremarkable except for dizziness and drowsiness after the 120-mg codeine dose. These findings suggest that flurbiprofen as an analgesic for patients with postpartum uterine pain is equivalent to aspirin and superior to codeine.

Adult↗

Determination of codeine in human plasma by high-performance liquid chromatography with fluorescence detection.

A rapid, reliable and rugged assay for determining codeine in human plasma using reversed-phase high-performance liquid chromatography with fluorescence detection was developed. This analytical method utilized an ion-exchange/mixed-mode solid-phase extraction procedure. The chromatographic separation was achieved using a 150 x 4.6 mm I.D., 3-microns reversed-phase C8 (deactivated for basic analytes) column at ambient temperature. Fluorescence detection (excitation at 214 nm and emission above 345 nm) for codeine and nalorphine allowed for a detectable limit of 5 ng/ml. The results showed that the method was linear from 10 to 300 ng/ml. The method had good reproducibility, precision, accuracy and recoveries of 91 and 90% for codeine and nalorphine, respectively. This method has been applied to study the pharmacokinetics of codeine in normal human subjects.

Chromatography, High Pressure Liquid↗

Codeine: developmental toxicity in hamsters and mice.

Timed-pregnant LVG Syrian hamsters and Swiss CD-1 mice were dosed orally twice daily (b.i.d.) with codeine in water on Gestational Days (gd) 5-13 (0, 10, 50, or 150 mg/kg, b.i.d.--hamsters) or 6-15 (0, 37.5, 75, 150, or 300 mg/kg, b.i.d.--mice). Dams were necropsied on gd 14 (hamsters) or 17 (mice), and fetuses were weighed, sexed, and examined for external, visceral, and skeletal malformations. No maternal deaths were observed in hamsters, while 19% of the pregnant mice in the high-dose group died. Maternal weight gain (gestational and treatment periods) and gravid uterine weights were significantly depressed in hamsters (150 mg/kg, b.i.d.) and in mice (300 mg/kg, b.i.d.). However, the corrected weight gain for both species, although decreased, was not significantly different from that of the controls. In both species, maternal liver weights (relative) were significantly increased in the high-dose groups. There were increases in the percentage resorptions per pregnant dam and in the proportion of litters with 100% resorptions in the high-dose groups of both species. Considering only live litters, the number of live fetuses per litter and the sex ratio were unaffected in both species. Mean fetal body weights were also significantly decreased in the 50 and 150 mg/kg, b.i.d. (hamsters), and the 150 and 300 mg/kg, b.i.d. (mice), groups. The no-observed-adverse-effect levels (NOAELs) for developmental toxicity were 10 (hamsters) and 75 (mice) mg/kg, b.i.d., whereas the NOAELs for maternal toxicity were 50 (hamsters) and 150 (mice) mg/kg, b.i.d. The predominant structural malformation in hamsters was meningoencephalocele (high-dose group only), affecting 3% of fetuses and 19% of litters (neither statistically significant). Codeine did not induce any increase in structural malformations in mice. Thus, codeine produced developmental toxicity (as indicated by decreased fetal body weight) at doses below those producing maternal toxicity in both hamsters and mice. In the hamster, the more sensitive species to codeine developmental toxicity, effects were observed at a total daily dose of 100 mg/kg, which is only 11 times the maximum human therapeutic oral dose.

Abnormalities, Drug-Induced↗

Efficacy and quality of ibuprofen and acetaminophen plus codeine analgesia.

Ibuprofen, 400 mg, was compared with 300 mg acetaminophen plus 30 mg of codeine and placebo in 120 post-orthopedic surgery patients with moderate to severe pain. The study was designed as a double-blind, single-dose, parallel-group analgesic efficacy assay. Estimates of analgesia were obtained up to 6 h using categorical and visual analog measures of pain intensity and pain relief. Estimates of selected elements of mood and of sensory and affective components of pain were obtained at 0 and 2 h using contrasting mood word/phrase pairs and a portion of the McGill Pain Questionnaire, respectively. Drugs were distinguishable from placebo in total analgesic effect, and ibuprofen was more effective than acetaminophen plus codeine, especially in terms of duration. While peak effects were comparable, they occurred 1 h later following ibuprofen. Differences among treatments were more discernible using visual analog measures. Side effects were minimal. Ibuprofen provided greater improvement in selected elements of mood than acetaminophen plus codeine at comparable levels of pain relief. While decreases in the sensory component of pain were most highly associated with pain relief provided by ibuprofen, decreases in the affective component were most highly associated with pain relief following acetaminophen plus codeine. These latter results indicate that mood assessment and the discrimination between sensory and affective components of pain could be particularly useful within analgesic drug assays, especially when comparing analgesics of differing pharmacologic class and when comparing the results of such assays in pain syndromes characterized by differing pain quality.

Acetaminophen↗

Ibuprofen plus codeine, ibuprofen, and placebo in a single- and multidose cross-over comparison for coxarthrosis pain.

The analgesic efficacy of 200 mg ibuprofen plus 30 mg codeine, 200 mg ibuprofen and placebo was investigated in a new analgesic evaluation model using single- and repeated-dose administration. The study was a double-blind randomized cross-over investigation in 26 coxarthrosis patients with persistent pain. After a washout period of at least 2 days with paracetamol available as rescue analgesic, each of the 3 treatments was administered in a total of 6 doses during 24 h. The hourly pain intensity was recorded on a 100-mm visual analogue scale (VAS) for 8 h after the 1st and the 6th dose. The pretreatment VAS score was 31-37 mm. After the 1st dose the 8-h mean pain intensity values were 25, 27, and 26 mm after ibuprofen plus codeine, ibuprofen, and placebo, respectively. Following another 5 doses every 4 h the corresponding values were 10, 17 and 29 mm. Repeated administration of both active drugs reduced the pain intensity significantly. The analgesic efficacy of ibuprofen plus codeine was significantly superior to that of ibuprofen which was, in turn, superior to that of placebo. In conclusion, analgesic efficacy was better differentiated after repeated-dose than after single-dose administration. The present study design was able to differentiate between 200 mg ibuprofen plus 30 mg codeine and 200 mg ibuprofen alone in a relatively small number of patients.

Adult↗

Dose-response inhibition of rat compound nerve action potential by dextropropoxyphene and codeine compared to morphine and cocaine in vitro.

1. The effects of dextropropoxyphene hydrochloride (dextropropoxyphene) codeine phosphate (codeine), morphine hydrochloride (morphine), and cocaine hydrochloride (cocaine) on the compound action potentials (cAP) of the rat phrenic nerve were studied in vitro. 2. Dextropropoxyphene, cocaine, codeine and morphine depressed the cAP in a reversible, dose-dependent way. After 60 min exposure to the drugs, dextropropoxyphene, inhibited the cAP between 0.025 and 0.5 mM, cocaine between 0.01 and 5 mM, codeine between 0.1 and 10 mM and morphine between 0.5 and 70 mM. The inhibition caused by 5 mM morphine could not be reversed by naloxone. 3. Dextropropoxyphene demonstrated the most potent cAP inhibition compared to the other drugs tested. The observed dose range for the inhibition of the cAP of rat phrenic nerve includes that observed after intoxications with dextropropoxyphene (0.004-0.06 mM) in the clinic. 4. For all other drugs tested the present observed dose ranges are much greater than the plasma concentrations previously reported after therapeutic use and intoxication.

Action Potentials↗

Gas chromatography with surface ionization detection: a highly sensitive method for determining underivatized codeine and dihydrocodeine in body fluids.

Underivatized codeine and dihydrocodeine in human plasma and urine have been determined with a high degree of accuracy by capillary gas chromatography (GC) with surface ionization detection (SID). The drugs were extracted with the aid of Sep-Pak C18 cartridges. Recovery of both drugs was > or = 90%. The calibration curves obtained with dimemorfan as an internal standard showed linearity in the range 4.5-72.3 and 3.0-75.5 ng/ml of plasma for codeine and dihydrocodeine, respectively. The detection limit was about 100 pg on column (2.5 ng/ml sample). Codeine was determined quantitatively in plasma and urine obtained from a volunteer who had received 10 mg codeine phosphate orally 3 h before the sampling: the levels were found to be 14.1 and 142 ng/ml, respectively. The present GC-SID method has been compared carefully with GC-NPD (nitrogen-phosphorus detection) using the same extracts; the sensitivity of GC-SID was more than ten times greater than that of GC-NPD, with background noise correspondingly lower.

Adult↗

Physostigmine, galanthamine and codeine act as 'noncompetitive nicotinic receptor agonists' on clonal rat pheochromocytoma cells.

The acetylcholine esterase inhibitor (-)-physostigmine has been shown to act as agonist on nicotinic acetylcholine receptors from muscle and brain, by binding to sites on the alpha-polypeptide that are distinct from those for the natural transmitter acetylcholine (Schröder et al., 1994). In the present report we show that (-)-physostigmine, galanthamine, and the morphine derivative codeine activate single-channel currents in outside-out patches excised from clonal rat pheochromocytoma (PC12) cells. Although several lines of evidence demonstrate that the three alkaloids act on the same channels as acetylcholine, the competitive nicotinic antagonist methyllycaconitine only inhibited channel activation by acetylcholine but not by (-)-physostigmine, galanthamine or codeine. In contrast, the monoclonal antibody FK1, which competitively inhibits (-)-physostigmine binding to nicotinic acetylcholine receptors, did not affect channel activation by acetylcholine but inhibited activation by (-)-physostigmine, galanthamine and codeine. The three alkaloids therefore act via binding sites distinct from those for acetylcholine, in a 'noncompetitive' fashion. The potency of (-)-physostigmine and related compounds to act as a noncompetitive agonist is unrelated to the level of acetylcholine esterase inhibition induced by these drugs. (-)-Physostigmine, galanthamine and codeine do not evoke sizable whole-cell currents, which is due to the combined effects of low open-channel probability, slow onset and slow inactivation of response. In contrast, they sensitize PC12 cell nicotinic receptors in their submaximal response to acetylcholine. While the abundance of nicotinic acetylcholine receptor isoforms expressed in PC12 cells excludes identification of specific nicotinic acetylcholine receptor subtypes that interact with noncompetitive agonists, the identical patterns of single-channel current amplitudes observed with acetylcholine and with noncompetitive agonists suggested that all PC12 cell nicotinic acetylcholine receptor subtypes that respond to acetylcholine also respond to noncompetitive agonist. The action of noncompetitive agonists therefore seems to be highly conserved between nicotinic acetylcholine receptor subtypes, in agreement with the high level of structural conservation in the sequence region harboring major elements of this site.

Acetylcholine↗

Optimization of a capillary zone electrophoresis method by using a central composite factorial design for the determination of codeine and paracetamol in pharmaceuticals.

Capillary zone electrophoresis was optimized to quantitatively determine codeine and paracetamol via central composite factorial design. Critical parameters (concentration, buffer, pH, voltage) assessed effects on resolution, analysis time and efficiencies. Optimum separation conditions were achieved using phosphate buffer 20 mM (pH 6.8) and voltage (15 kV). The optimized procedure easily determined codeine and paracetamol with separation in less than 3 min. Calibration curves (R > 0.999) were prepared, with LODs of 13.5 and 340 ng mL(-1) for codeine and paracetamol, respectively, and a good R.S.D.% (<3%). This method was applied to determine codeine and paracetamol in pharmaceutical formulations; recoveries coincided with stated contents.

Acetaminophen↗

Synergistic effects between codeine and diclofenac after local, spinal and systemic administration.

This study was designed to evaluate the extent of the antinociceptive interaction between codeine and diclofenac at the local, spinal and systemic level. The effects of individual and fixed-ratio combinations of locally, spinally or orally given codeine and diclofenac were assayed using the formalin test in rats. Isobolographic analysis was employed to characterize the synergism produced by the combinations. Codeine, diclofenac and fixed-ratio codeine-diclofenac combinations produced a dose-dependent antinociceptive effect when administered locally, spinally or systemically. ED(30) values were estimated for the individual drugs and isobolograms were constructed. Theoretical ED(30) values for the combination estimated from the isobolograms were 422.2+/-50.5 microg/paw, 138.5+/-9.2 microg/rat, and 9.3+/-1.1 mg/kg for the local, spinal and oral routes, respectively. These values were significantly higher than the actually observed ED(30) values which were 211.1+/-13.6 microg/paw, 45.9+/-3.9 microg/rat, and 2.5+/-0.2 mg/kg, indicating a synergistic interaction. Systemic administration resulted in the highest increase in potency, being about fourfold, while spinal and local administration increased potency in two- and threefold, respectively. The fact that the highest synergism was observed after systemic administration suggests that the interaction is occurring at several anatomical sites. The results support the clinical use of this combination in pain management.

Administration, Oral↗

Probable activation of the opioid receptor-nitric oxide-cyclic GMP-K+ channels pathway by codeine.

There is evidence that local peripheral administration of morphine produces antinociception through the activation of the nitric oxide (NO)-cyclic GMP-K(+) channels pathway. Therefore we evaluated the possible participation of this pathway in the antinociceptive action produced by codeine in the rat 5% formalin test. Local peripheral injection of codeine produced a dose-dependent antinociception during the first and second phases of the test. Local pretreatment of the paws with the NO synthase inhibitor N(G)-L-nitro-arginine methyl ester (L-NAME), the soluble guanylyl cyclase inhibitor methylene blue, the ATP-sensitive K(+) channel inhibitors glibenclamide and tolbutamide, the non-selective voltage-gated K(+) channel inhibitors 4-aminopyridine (4-AP) and tetraethylammonium (TEA) and the opioid receptor blocker naloxone prevented codeine-induced antinociception in both phases of the test. L-NAME, methylene blue, K(+) channel blockers and naloxone by themselves did not modify formalin-induced nociceptive behavior. Our data suggest that codeine could activate the opioid receptor-NO-cyclic GMP-K(+) channels pathway in order to produce its peripheral antinociceptive effect in the formalin test.

4-Aminopyridine↗

Structure investigation of codeine drug using mass spectrometry, thermal analyses and semi-emperical molecular orbital (MO) calculations.

Codeine is an analgesic with uses similar to morphine, but it has a mild sedative effect. It is preferable used as phosphate form and it is often administrated by mouth with aspirin or paracetamol. Therefore, it is important to investigate its structure to know the active groups and weak bonds responsible for its medical activity. Consequently in the present work, codeine was investigated by mass spectrometry and thermal analyses (TG, DTG and DTA) and confirming by semi-empirical MO-calculation (PM3 method) in the neutral and positively charged forms of the drug. Some results of studying the d-block element complexes of codeine were used to declare the relationship between drug structure and its chemical reactivity in vitro system. The mass spectra and thermal analyses fragmentation pathways were proposed and compared to each other to select the most suitable scheme representing the correct fragmentation of this drug. From EI mass spectra, the main primary cleavage site of the charged drug molecule is that due to beta-cleavage to nitrogen atom in its skeleton. It occurs in two parallel mechanisms with the same possibility, i.e. no difference in appearance activation energy between them. In the neutral drug form the primary site cleavage is that occurs in the ether ring. Thermal analyses of the neutral form of the drug revealed the high response of the drug to the temperature variation with very fast rate. It decomposed in several sequential steps in the temperature range 200-600 degrees C. The initial thermal fragments are very similar to that obtained by mass spectrometric fragmentation. Therefore, comparison between mass and thermal helps in selection of the proper pathway representing the fragmentation of this drug. This comparison successfully confirmed by MOC. These calculations give the bond order, charge distribution, heat of formation and possible hybridization of some atoms in different position of the drug skeleton. This helps the successful choice of the weakest bond at which both mass and thermal fragmentation occurs. Therefore, the best fragmentation pathway of this drug is correctly selected. The effect of such fragmentation on the drug behavior in the human body can be expected as a result of comparing these data with that obtained on studying codeine metal complexes using mass and thermal fragmentation techniques.

Carbon Radioisotopes↗

Differential effect of codeine on coughs caused by mechanical stimulation of two different sites in the airway of guinea pigs.

We studied the difference in the effects of codeine on coughs caused by mechanical stimulation to the larynx and to the bifurcation of the trachea in lightly anaesthetized guinea pigs. Mechanical stimulation to the larynx or the bifurcation of trachea caused a stable cough response. The response was reproducible over 60 min, when stimulation was repeatedly applied at 20-min intervals. No significant difference was found between the amplitudes of the responses to mechanical stimulation of the larynx and of the tracheal bifurcation. Codeine, 10, 20 and 50 mg/kg, dose dependently depressed the coughs caused by larynx stimulation. The antitussive, however, failed to depress the cough caused by stimulation to the tracheal bifurcation, although a large dose, 50 mg/kg, significantly depressed the cough. In capsaicin-treated guinea pigs, codeine at 20 mg/kg significantly depressed the cough caused by stimulation to the tracheal bifurcation. The present results suggest that cough caused by mechanical stimulation to the larynx might be more sensitive to codeine treatment than cough caused by stimulation to the bifurcation of trachea. Furthermore, it is suggested that coughs caused by mechanical stimulation to both sites might consist of at least two components as regards their pharmacological nature.

Animals↗

Combination hydrocodone and ibuprofen versus combination codeine and acetaminophen for the treatment of chronic pain.

OBJECTIVE: The objective of this study was to compare the effectiveness of combination hydrocodone 7.5 mg and ibuprofen 200 mg with that of combination codeine 30 mg and acetaminophen 300 mg for the treatment of chronic pain. BACKGROUND: Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen. METHODS: In this randomized, parallel-group, double-blind, repeated-dose, active-comparator, 4-week, multicenter study, 469 patients were randomly assigned to receive a 1-tablet (n = 156) or 2-tablet (n = 153) dose of combination hydrocodone 7.5 mg and ibuprofen 200 mg (HI1 and HI2, respectively) or a 2-tablet dose of combination codeine 30 mg and acetaminophen 300 mg (CA, n = 160), the active comparator, every 6 to 8 hours as needed for pain. Efficacy was measured through pain relief scores, number of daily doses of study medication, number of daily doses of supplemental analgesics, number of patients who discontinued therapy due to an unsatisfactory analgesic response, and global assessment scores. RESULTS: Of the 469 patients, 255 (54.4%) were female and 214 (45.6%) were male. The mean age was 51.1 years. Types of chronic pain included back (214; 45.6%), arthritic (145; 30.9%), other musculoskeletal (65; 13.9%), cancer (6; 1.3%), diabetic neuropathic (3; 0.6%), postherpetic neuralgic (5; 1.1%), other neurologic (21; 4.5%), and other unclassified chronic pain (10; 2.1%). During the 48 hours prior to the study, 351 (74.8%) patients had been treated with opioid or opioid-nonopioid combination analgesics. The overall mean daily pain relief score was significantly greater in the HI2 group (2.25+/-0.89) than in the HI1 group (1.98+/-0.87) (P = 0.003) or the CA group (1.85+/-0.96) (P < 0.001). The overall mean number of daily doses of study medication was significantly less in the HI2 group (2.94+/-0.99) than in the HI1 group (3.23+/-0.76) (P = 0.036) or the CA group (3.26+/-0.75) (P = 0.014). The overall mean number of daily doses of supplemental analgesics was significantly less in the HI2 group (0.24+/-0.49) than in the HI1 group (0.34+/-0.58) (P = 0.021) or CA group (0.49+/-0.85) (P = 0.010). The number of patients who discontinued treatment due to an unsatisfactory analgesic response was significantly less in the HI2 group (2; 1.3%) than in the CA group (12; 7.5%) (P = 0.008). HI2 was more effective than HI1 and CA as measured by pain relief scores for week 1 (P < 0.001 vs HI1 and CA), week 2 (P < 0.001 vs HI1 and CA), and week 3 (P = 0.008 vs HI1 and P < 0.001 vs CA); daily doses of study medication for week 1 (P = 0.019 vs HI1 and P = 0.011 vs CA); daily doses of supplemental analgesics for week 1 (P = 0.010 vs HI1 and CA); and global assessment scores for week 1 (P = 0.018 vs HI1 and P < 0.001 vs CA), week 2 (P = 0.005 vs HI1 and P < 0.001 vs CA), and week 4 (P = 0.013 vs HI1 and P = 0.023 vs CA). There were no significant differences between HI1 and CA in any efficacy variable. There were no significant differences in the number of patients experiencing adverse events in the HI2 (127; 83%), HI1 (124; 79.5%), and CA (129; 80.6%) groups. However, the mean number of patients who discontinued treatment due to adverse events was significantly greater in the HI2 group (40; 26.1%) than in the HI1 group (23; 14.7%) (P = 0.013). CONCLUSIONS: The results of this study suggest that 2-tablet doses of combination hydrocodone 7.5 mg and ibuprofen 200 mg may be more effective than either 1-tablet doses of this combination or 2-tablet doses of combination codeine 30 mg and acetaminophen 300 mg. Moreover, 1-tablet doses of combination hydrocodone 7.5 mg and ibuprofen 200 mg may be as effective as 2-tablet doses of combination codeine 30 mg and acetaminophen 300 mg.

Acetaminophen↗

Excessive grooming induced by the administration of codeine and morphine.

Previous studies have shown that peripheral injections of the codeinone RX 336-M can induce excessive grooming in rats in an age-dependent fashion. The present experiment demonstrates that codeine, itself, also induces excessive grooming but with apparent equal effectiveness at all ages tested. Because of the structural similarity between codeine and morphine, the effects of intraperitoneally administered morphine were examined as well. Morphine was found to produce a temporal course of excessive grooming quite different from that produced by codeine. Morphine did not affect grooming in the first half (30 min) of the observation period, but accentuated it, briefly, for the next 30-45 min. Intraventricular administration of codeine at doses of 0.3 or 1.0 microgram/3 microliter had no effect on grooming in animals previously shown to demonstrate excessive grooming in response to either dose.

Aging↗