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PubMed1981

Aspirin and acetaminophen as constituents of analgesic combinations.

Aspirin and acetaminophen are the mainstays of oral analgesic combinations. One group of combinations is composed of antipyretic-analgesics combined with each other. The superior efficacy of such combinations as compared with an optimal dose of one of the constituents remains to be proved, and there is little evidence that such combinations have less adverse-effect liability than a single agent. On the other hand, there is substantial evidence that combinations of an optimal dose of aspirin or acetaminophen with a narcotic (eg, codeine, hydrocodone, or oxycodone) produce an additive analgesic effect greater than that obtained by doubling the dose of either constituent administered alone. There is also some evidence that the adverse effects produced by such combinations are less than would be produced by an equianalgesic dose of a single constituent.

Acetaminophen↗

PubMed2002

Hydromorphone for acute and chronic pain.

BACKGROUND: While morphine is the gold standard for the management of severe cancer pain, some patients either do not achieve adequate analgesia, or suffer intolerable morphine-related toxicity. For these patients alternatives such as hydromorphone are recommended. However, there appear to be gaps in our understanding of the efficacy and potency of hydromorphone. OBJECTIVES: This review explores and assesses the evidence for the efficacy of hydromorphone in the management of pain. SEARCH STRATEGY: Randomised trials which included hydromorphone were sought using electronic databases and by handsearching relevant journals. Date of the most recent search: February 2000. SELECTION CRITERIA: RCTs which involved the administration of hydromorphone, for both acute and chronic pain conditions, in adults and children, were included. DATA COLLECTION AND ANALYSIS: A data extraction form was designed for the purpose of the review. The validity of each trial for inclusion was assessed using criteria described in the Cochrane Handbook. A grade was allocated to each study on the basis of allocation concealment. A checklist was used to assess blinding. MAIN RESULTS: Forty three studies (2725 subjects) were included in the review. Approximately half of these studies received a low quality score. In addition, the heterogeneity of the studies precluded combination of data and results. A meta-analysis was therefore not possible. Of the 43 included studies, 11 (645 subjects) involved chronic pain conditions (all cancer) and 32 (2080 subjects) acute pain. Three studies were placebo-controlled. Of the remainder, hydromorphone was compared with other opioids (morphine, fentanyl, sufentanyl, meperidine, oxycodone, diamorphine), bupivicaine and with itself, using different formulations. The routes of administration included intravenous, oral, spinal, intramuscular and subcutaneous. Overall, hydromorphone appears to be a potent analgesic. The limited number of studies available suggest that there is little difference between morphine and hydromorphone in terms of analgesic efficacy, adverse effect profile and patient preference. However, as most studies involved small numbers of patients, it is difficult to determine real differences between both drugs. In the context of both acute and chronic pain, the issue of equi-analgesic ratios between morphine and hydromorphone was not resolved. REVIEWER'S CONCLUSIONS: The studies included in this review were varied in terms of quality and methodology. However, the majority demonstrated that hydromorphone is a potent analgesic, that the clinical effects of hydromorphone appear to be dose-related, and that the adverse effect profile of hydromorphone is similar to that of other mu opioid receptor agonists.

Acute Disease↗

PubMed2005

Opioid use by patients in an orthopedics spine clinic.

OBJECTIVE: Concerns regarding the efficacy, toxicity, tolerance, dependence, and abuse of opioids have limited their use for patients with chronic spine pain. In our previous study of rheumatology clinic patients, opioid analgesics were found to be highly effective, produced only mild side effects, and had few instances of opioid abuse. The purpose of this study was to replicate our previous study in another large cohort of patients with nonmalignant pain due to well-defined spinal diseases. METHODS: Opioid use was studied in 230 orthopedics spine clinic patients by retrospective analysis of prescriptions for 3 years and cross-sectional analysis of efficacy and toxicity by patient interviews. Opioid use and stability of the daily dose over 3 years were derived from computerized pharmacy records. Medical records, operative reports, and radiographic studies were reviewed to determine the reason for dosage escalations and to detect instances of abuse or addiction behaviors. Patients were interviewed to determine the efficacy, frequency, and types of side effects and instances of obtaining opioids from sources outside the Veterans Affairs system. RESULTS: Opioids were prescribed for 152 of the 230 patients, for < 3 months (short-term [STO]) in 94, > or =3 months (long-term [LTO]) in 58, and none in 72 (no opioid [NTO]). Medications prescribed were codeine, oxycodone, propoxyphene, tramadol, morphine, meperidine, fentanyl, or hydroxycodone, either alone or in combination. Interviews were completed in 72 STO, 50 LTO, and 45 NTO patients. Pain severity (0-10 scale) was not different in patients with different spinal pathologies. Opioids significantly reduced the back pain severity score from 8.3 +/- 1.5 to 4.5 +/- 2.2 (mean +/- SD). Mild side effects (most commonly, constipation and sedation) were reported by 58% of the opioid-treated patients but rarely caused them to stop taking the medication. There was no significant increase from the mean +/- SD initial opioid dosage of 5.0 +/- 12.2 30-mg codeine equivalents per day (30 mg oral codeine = 5 mg oral morphine) to the mean peak dosage of 7.9 +/- 12.5 and the mean recent dosage of 4.3 +/- 6.3, suggesting that tolerance to opioid analgesia did not appear to occur in these patients. Dosage escalations of > 2 30-mg codeine equivalents occurred 19 times in 17 LTO patients and was due to worsening of the underlying painful condition, complications of spine surgery, or unrelated surgical or medical problems in all but 3 of them (5%). These 3 patients also displayed other abuse behaviors. Abuse behaviors were not more frequent in those with or without a history of abuse/addiction. CONCLUSION: This study provides data on the efficacy, toxicity, tolerance, and abuse or addiction behaviors with opioid therapy in a large cohort of patients in an orthopedics spine clinic. The results provide objective data from patients with well-defined spine diagnoses to challenge the position that opioid treatment is inappropriate for chronic nonmalignant pain. This study provides clinical evidence to support and protect physicians treating patients with chronic musculoskeletal diseases, who may be reluctant to prescribe opioids because of possible sanctions from regulatory agencies. More important, it will benefit patients by permitting them to receive these effective, safe medications.

Aged↗

PubMed2006

Treatment of pain in juvenile idiopathic arthritis: a survey of pediatric rheumatologists.

OBJECTIVE: To assess the opinions and current practice of pediatric rheumatologists regarding treatment of chronic pain in children with juvenile idiopathic arthritis (JIA). METHODS: Standardized questionnaires were distributed to pediatric rheumatologists who are members of the Children's Arthritis and Rheumatology Research Alliance. Demographic data, opinions, and attitudes were solicited about pain assessment, current treatment of JIA with residual pain, and actual use of opioids to treat pain in children with JIA. RESULTS: Of 99 rheumatologists who were contacted, 53 responses were received (53.5%). No significant demographic differences were found in attitudes about pain management and use of opioids. A total of 77.3% of respondents agreed that there are patients who continue to have significant pain despite adequate treatment. However, 59.6% disagreed with the use of opioid analgesics for treatment of those patients. Cross tabulations showed significant relationships between attitudes about opioid use and concerns for side effects, including drowsiness, fatigue, and constipation (chi(2) = 1.16, P > 0.05), as well as addiction (chi(2) = 5.51, P = 0.019). Thirty percent of those who strongly disagreed with opioid use and 52.4% of those who disagreed had in fact prescribed opioids in the past year. The most commonly prescribed opioids were codeine and oxycodone. Practitioners' perceived knowledge of the drugs significantly affected their likelihood to prescribe them. CONCLUSION: Pediatric rheumatologists are divided in their attitudes regarding treatment of residual pain in children with JIA. Concern for side effects appears to be a major factor in the decision to prescribe these analgesics. More data are needed to facilitate clearer cost-benefit analyses in the decision to prescribe opioids to this clinical population.

Adult↗

PubMedDate not supplied

Critical review of oral drug treatments for diabetic neuropathic pain-clinical outcomes based on efficacy and safety data from placebo-controlled and direct comparative studies.

The present review aims to evaluate the efficacy and safety of a selection of oral treatments for the management of painful diabetic neuropathy. A literature review was conducted retrieving placebo-controlled and direct comparative studies with a selection of oral treatments for painful diabetic neuropathy. All studies were analyzed with regard to efficacy and tolerability. Efficacy was evaluated as the percentage improvement in pain intensity between baseline and endpoint. Tolerability was evaluated by means of study discontinuations due to adverse events and by incidence of drug-related adverse events. The analyzed trials enrolled different patient populations with mostly small numbers of patients. The great variability in dosages and dose titration schemes, cross-over designs with variable wash-out periods, and other design schemes made comparison between the different studies difficult. Gabapentin, lamotrigine, tramadol, oxycodone, mexiletine, and acetyl-L-carnitine were the only treatments studied in large (at least 100 patients), placebo-controlled parallel group trials.It is concluded that standardization in design and reporting for comparison of treatments is needed. Validated questionnaires for evaluation of the efficacy and safety should be further developed. Based on the reviewed randomised controlled trials, gabapentin shows good efficacy, a favourable side-effect profile with lack of drug interactions and therefore it may be a first choice treatment in painful diabetic neuropathy, especially in the elderly. However, head to head trials of current treatments are lacking and therefore randomized controlled trials are required to address this issue.

Administration, Oral↗

PubMed2004

Capillary electrophoresis analysis of a wide variety of seized drugs using the same capillary with dynamic coatings.

Capillary electrophoresis methodology is presented for the routine analysis of a wide variety of seized drugs using the same capillary with dynamic coatings and multiple run buffers. The types of exhibits analyzed using diode array UV detection include phenethylamines, cocaine, oxycodone, heroin, lysergic acid diethylamide (LSD), opium, hallucinogenic mushrooms, and gamma-hydroxybutyrate-gamma-butyrolactone (GHB-GBL). Both qualitative and quantitative analyses are achieved using run buffers that contain additives that provide for secondary equilibrium and/or dynamic coating of the capillary. Dynamic coating of the capillary surface is accomplished by rapid flushes of 0.1 N sodium hydroxide, water, buffer containing polycation coating reagent, and a buffer containing a polyanionic coating reagent (with or without cyclodextrin(s)) or a micelle coating reagent. Dynamic coating with a polyanionic coating reagent is used for the analysis of moderately basic seized drugs and adulterants. The use of cyclodextrin in the run buffer not only allows for chiral analysis but also greatly enhances separation selectivity for achiral solutes. A capillary dynamically coated with a micelle allows for the analysis of neutral, acidic, and weakly basic drugs (GHB, GBL and neutral, acidic, and weakly basic adulterants). Dynamic coating, which gives rise to a relatively high and robust electroosmotic flow at pH < 7, allows for rapid, precise and reproducible separations. For a wide variety of drugs, excellent linearity and migration time precision and good peak area precision (external and internal standard) is obtained. Quantitative results for synthetic mixtures are in good agreement with actual values. Screening for adulterants is greatly enhanced by the use of automated library searches.

Alkaloids↗

PubMed2006

Capillary electrophoresis contributions to the hydromorphone metabolism in man.

CE-ESI multistage IT-MS (CE-MS(n), n < or = 4) and computer simulation of fragmentation are demonstrated to be effective tools to detect and identify phase I and phase II metabolites of hydromorphone (HMOR) in human urine. Using the same CE conditions as previously developed for the analysis of urinary oxycodone and its metabolites, HMOR and its phase I metabolites produced by N-demethylation, 6-keto-reduction and N-oxidation and phase II conjugates of HMOR and its metabolites formed with glucuronic acid, glucose, and sulfuric acid could be detected in urine samples of a patient that were collected during a pharmacotherapy episode with daily ingestion of 48 mg of HMOR chloride. The CE-MS(n) data obtained with the HMOR standard, synthesized hydromorphol and hydromorphone-N-oxide, and CYP3A4 in vitro produced norhydromorphone were employed to identify the metabolites. This approach led to the identification of previously unknown HMOR metabolites, including HMOR-3O-glucide and various N-oxides, structures for which no standard compounds or mass spectra library data were available. Furthermore, the separation of alpha- and beta-hydromorphol, the stereoisomers of 6-keto-reduced HMOR, was achieved by CE in the presence of the single isomer heptakis(2,3-diacetyl-6-sulfato)-beta-CD. The obtained data indicate that the urinary excretion of alpha-hydromorphol is larger than that of beta-hydromorphol.

Analgesics, Opioid↗

PubMed2006

An automated and fully validated LC-MS/MS procedure for the simultaneous determination of 11 opioids used in palliative care, with 5 of their metabolites.

A fully validated liquid chromatographic procedure coupled with electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) is presented for quantitative determination of the opioids buprenorphine, codeine, fentanyl, hydromorphone, methadone, morphine, oxycodone, oxymorphone, piritramide, tilidine, and tramadol together with their metabolites bisnortilidine, morphine-glucuronides, norfentanyl, and nortilidine in blood plasma after an automatically performed solid-phase extraction (SPE). Separation was achieved in 35 min on a Phenomenex C12 MAX-RP column (4 microm, 150 x 2 mm) using a gradient of ammonium formiate buffer (pH 3.5) and acetonitrile. The validation data were within the required limits. The assay was successfully applied to authentic plasma samples, allowing confirmation of the diagnosis of overdose situations as well as monitoring of patients' compliance, especially in patients under palliative care.

Analgesics, Opioid↗

PubMed2005

Rates of abuse of tramadol remain unchanged with the introduction of new branded and generic products: results of an abuse monitoring system, 1994-2004.

PURPOSE: The analgesic Tramadol HCl (Ultram) was approved in 1994 as a non-scheduled drug under the CSA provided that a novel risk-management program would be developed by an Independent Steering Committee (ISC). The risk-management program began in 1995 with the launch of Ultram, and has been modified over the past decade to accommodate Ultracet (Ultram and acetaminophen) in 2001 and generic tramadol in 2002. This provided a unique opportunity to study the potential changes in abuse as the generic and combination products became available. METHODS: To proactively detect cases of abuse and diversion, the ISC developed a comprehensive questionnaire which was completed quarterly by an extensive network of drug abuse experts (n = 309) and police agencies (n = 100) who were asked to indicate how many diversion cases involving Ultram, Ultracet, and generic tramadol were identified during the preceding 3 months and what were the ten most commonly diverted drugs in their catchment area during that period. RESULTS AND CONCLUSIONS: The data generated demonstrate that the abuse of tramadol remained very low despite new branded and generic formulations. Contrary to the hypothesis that cheaper generic drugs would lead to higher rates of abuse, we found no increase in abuse with the introduction of generic tramadol. Ultracet abuse rates, unlike those found with other widely used hydrocodone and oxycodone combination products, have been even lower than that observed for tramadol. Since the FDA has now mandated that proactive risk-management plans be implemented for new drugs, the tramadol risk-management plan may be useful as a prototypic model which can be modified to accommodate other drugs with abuse potential.

Acetaminophen↗

PubMed1994

Pharmacological management of chronic pain: a clinician's perspective.

Of the currently available mu agonist drugs, the following are relatively contraindicated: 1. Methadone--unpredictable duration of action [5]. 2. Pethidine--unwanted central effects, metabolised to an active metabolite and too short acting. 3. Codeine--too weak and with constipating side-effects. 4. Fentanyl--too short acting. 5. Oxycodone--too short acting although suppositories may overcome some theoretical disadvantages. 6. Dextropropoxyphene--weak agonist which is possibly metabolised to a cardiotoxic metabolite [6]. Morphine remains the drug of choice for chronic pain when administered in a sustained release preparation. MS Contin, a slow release oral formulation of morphine, is available and has a predictable duration of action lasting from 8-12 h, while improved formulations are about to be released in the near future in some countries. Prescribers need to take into account the relatively poor oral bioavailability of morphine when calculating the daily morphine dose.

Analgesics↗

PubMed2005

[Palliative pain therapy, cannabinoids].

Cancer pain treatment should follow the recommendations of the World Health Organisation. Treatment should be with oral application, regular application times and following the analgesic step-ladder. Non-opioids such as dipyrone or non-steroids are used for slight to moderate pain, step-2 opioids such as tramadol or tilidine/naloxone for moderate pain and step-3 opioids such as morphine, oxycodone or hydromorphone for severe pain. Transdermal application of fentanyl or buprenorphine offer a non-invasive parenteral alternative for patients with stable pain syndromes. Cannabinoids such as tetrahydrocannabinol offer a valuable add-on option for cancer patients with refractory pain, spasticity, nausea or appetite loss.

Analgesics↗

PubMed2006

Is there a ceiling effect of transdermal buprenorphine? Preliminary data in cancer patients.

OBJECTIVE: The aim of this preliminary study was to explore the possibility of using higher doses of transdermal buprenorphine (TD-BUP) than those commonly used and available as manufactured patches, which are based on the assumption that BUP may have a ceiling effect that has never been determined yet. MATERIALS AND METHODS: Ten patients who were already receiving TD-BUP (70 microg/h, which is about 1.6 mg/day) and were no longer responsive to this dosage were administered higher doses up to a maximum of 140 microg/h within 6 days, when the study was completed. RESULTS: In six patients, dose increments of TD-BUP were effective, and patients achieved adequate analgesia within 6 days. Four patients discontinued the treatment due to inefficacy of TD-BUP 140 microg/h and were switched to other opioids until achieving stabilization (oxycodone 320 and 400 mg/day, methadone 120 mg/day, transdermal fentanyl 200 microg/h). This group of patients required higher doses than those chosen for TD-BUP, underlying the need to escalate the dose rapidly, a modality not accomplished with transdermal drugs. Adverse effects did not change and were similar to those observed before increasing the dose of TD-BUP. On the basis of these preliminary data, patients requiring doses higher than 70 microg/h of TD-BUP, in the range of 105-140 microg/h, may still have an analgesic benefit without important consequences in terms of adverse effects. It cannot be excluded that even higher doses may be effective, as some patients required rapid titration with higher morphine equivalent doses, and according to the protocol, other opioids were provided to facilitate this process. Further studies should clarify the role and the benefit of TD-BUP in specific clinical circumstances.

Administration, Cutaneous↗

PubMed2004

[New pharmaceutical and invasive approaches in cancer pain therapy].

Recent developments of newer opioids are now alternatives to morphine hydrochloride. Fentanyl and buprenorphine can be administered as trans dermal therapeutic systems. Hydromorphone and oxycodone can be given orally with different adverse profiles compared to morphine hydrochloride. Invasive therapeutic options should be kept in mind for patients refractory or resistant to conventional analgesic approaches. These approaches are presented and discussed, especially the neurolytic blockade of the celiac plexus which is important in the therapy of visceral pain. Epidural and intrathecal morphine administration can be used in the treatment of severe cancer pain.

Administration, Cutaneous↗

PubMed1991

Irreversible blockade of the high and low affinity (3H) naloxone binding sites by C-6 derivatives of morphinane-6-ones.

C-6 derivatives--hydrazones, phenylhydrazones, dinitrophenylhydrazones, oximes and semicarbazones--of morphinane-6-ones were synthesized and their binding characteristics were studied on rat brain membranes. The dihydromorphinone and oxymorphone derivatives compete for the (3H)naloxone binding sites with high affinity, while the dihydrocodeinone and oxycodone derivatives are less potent. The affinity of the new compounds is decreased for the delta sites as compared to the parent ligands. The ligands bearing bulky substituents also bind with low affinity to the kappa sites. The modification decreased the Na(+)-index of compounds indicating their mixed agonist-antagonist character. The dihydromorphinone derivatives are all capable to block irreversibly the high affinity binding site of (3H)naloxone, whereas the dihydrocodeionone derivatives block irreversibly the low affinity site. A possible mechanism for the inhibition is suggested.

Affinity Labels↗

PubMedDate not supplied

Supersensitivity to opioid analgesics following chronic opioid antagonist treatment: relationship to receptor selectivity.

The effect of chronic opioid antagonist treatment on the analgesic potency of six opioid agonists was compared to changes in opioid receptor density and the selectivity of each agonist for mu (DAMGO), delta (DPDPE) and kappa (U69,593) opioid receptors. Mice were implanted SC with a 15-mg naltrexone or placebo pellet for 8 days. The pellets were removed and 24 h later, mice were sacrificed and binding studies were conducted, or mice were tested in analgesia (tail-flick) dose-response studies. All six analgesics acted as full agonists for both placebo and naltrexone-treated mice. Naltrexone increased the analgesic potency of methadone, etorphine, fentanyl, meperidine, and oxycodone by 1.9-3.2-fold. The analgesic potency of propoxyphene was not increased significantly (1.3-fold). In saturation binding studies in brain homogenate, naltrexone increased the Bmax of mu, delta, and kappa opioid receptors by 86, 43, and 33%, respectively, without altering Kd. Competition binding studies for each receptor type were conducted in brains from untreated mice, and KIs were determined for each agonist. All agonists had greatest selectivity toward mu compared with delta and kappa receptors. There did not appear to be an obvious relationship between receptor selectivity and the magnitude of supersensitivity. These studies indicate that supersensitivity occurs for a broad range of opioid analgesics following chronic opioid antagonist treatment in the mouse. However, the selectivity of these agonists for mu, delta, and kappa receptors does not appear to correlate with differences in supersensitivity.

Analgesics↗

PubMed1989

Beneficial effects of psychiatric intervention on recovery after coronary artery bypass graft surgery.

The effects of perioperative psychiatric intervention were studied in 33 patients undergoing coronary artery bypass graft (CABG) surgery. All patients were evaluated preoperatively using the Mini-Mental State Exam and the Psychological Adjustment to Illness Scale-Self-Report. Participants in the study group (N = 16) had a structured psychiatric interview prior to surgery and were followed daily with supportive psychotherapy throughout their hospitalization. The number of medical complications was higher in the control group. No significant differences were found in neurologic or psychologic complications. The study group used significantly more oxycodone-acetaminophen (Percocet), but less morphine-sulfate or benzodiazepine on postoperative days 3, 4, and 6. The mean length of stay was 3 days shorter for patients in the study group. In the current era of escalating health care costs and high technology, clinical protocols and research studies that evaluate the cost effectiveness and efficacy of psychiatric intervention in medically ill patients should be pursued.

Adaptation, Psychological↗

PubMed1990

Influence of polarity on dose-response relationships of intrathecal opioids in rats.

Dose-response curves were constructed for intrathecal morphine (M), oxymorphone (OM), hydromorphone (HM), diamorphine (DM), 14-hydroxydihydromorphine (OHM), oxycodone (OC), hydrocodone (HC) and fentanyl (F). Intrathecal catheters were placed in 69 rats under halothane/N2O anaesthesia. After recovery, baseline hot plate and tail flick latencies were measured, and a dose of opioid was given. Hot plate and tail flick latencies were assessed at 5, 15, 30, 60, 90, 120 min and then hourly until they returned to within 25% of baseline. Response latencies were converted to per cent of maximum possible effect (% MPE) and the area under the % MPE X time curve was taken as the response. This measure includes information about both potency and duration of action. Each rat received 3 opioids and saline at intervals of 2-3 days. On a fifth occasion, the animal's first treatment was repeated. Each opioid was studied over an 8-fold dose range. Results of both hot plate and tail flick were best described by a model including log(dose), a component due to development of tolerance over the 5 experimental days, and an among-rat variation term. In the hot plate test, doses equieffective in producing a response (AUC) over the dose range studied were in the order OHM less than OM less than HM less than M less than F less than DM less than HC less than OC. Slopes of the log(dose)-response curves were similar for all drugs except OHM, which had a steeper slope. A model is proposed in which hot plate and tail flick latencies are prolonged while CSF concentrations of a drug are above its minimum effective concentration, and drug is cleared from the CSF by a first-order process, possibly uptake into the spinal cord and removal via the blood. This model predicts that log(dose)-response curves will be linear, as was observed, with slopes inversely proportional to the rate constant for clearance from CSF. According to this model the steeper slope of the OHM log(dose)-response may be interpreted as indicating slower clearance from CSF. OHM has the lowest octanol/pH 7.4 buffer distribution coefficient (0.34) of all opioids studied, possibly leading to a lower rate of uptake into the spinal cord.

Animals↗

PubMed1991

Differentiating analgesic and non-analgesic drug activities on rat hot plate: effect of behavioral endpoint.

The contribution of behavioral endpoint to results obtained in the 55 degrees C rat hot plate procedure was assessed. Specifically, the use of a hind paw lick-only endpoint was compared to that of a hind paw lick-or-jump endpoint. Effects of prototypical analgesic and non-analgesic compounds on response latency increases were determined under each condition. Whereas the effects of morphine, oxycodone and codeine were similar under each condition, effects of a number of non-analgesic agents differed markedly depending upon the endpoint used. Clozapine, chlorpromazine, thioridazine, atropine, scopolamine, benactyzine, yohimbine, idazoxan and cyproheptadine produced dose-dependent increases in response latency under the hind paw lick-only condition but did not increase latencies when the hind paw lick-or-jump endpoint was used. Haloperidol, sulpiride, benztropine, methyl atropine, phentolamine, prazosin, methiothepin, methysergide, diphenhydramine, pargyline and diazepam failed to increase response latencies under the hind paw lick-only condition. Moreover, whereas diazepam, chlorpromazine, pentobarbital, dantrolene and ethanol produced dose-dependent increases in the height required for successful aerial righting, increases in hind paw lick-or-jump latencies occurred only following near-anesthetic doses of pentobarbital and ethanol. These data indicate that the hind paw lick endpoint is susceptible to perturbation by extraneous pharmacologic activities. Drugs exerting muscarinic cholinergic and alpha 2-adrenergic antagonist effects are particularly able to disrupt this behavior. Disruption is not associated specifically with any other pharmacologic action, although other activities may interfere with the response. In contrast, the hind paw lick-or-jump endpoint fails to detect skeletal muscle relaxant activity and only detects gross motor impairment when near-anesthetic doses of drugs are used. The present data suggest that detection of non-analgesic drug activities by rat hot plate can be minimized by use of a hind paw lick-or-jump endpoint.

Analgesics↗