Opioid Preparations Research Articles

Fentanyl Buccal Tablet: Faster Rescue Analgesia For Breakthrough Pain?

Breakthrough pain (BTP) is an unmet clinical need that is still poorly diagnosed, evaluated and inadequately treated. The prevalence of BTP has been estimated to affect at least 64% of cancer patients. Two pain-relief strategies were proposed: preventive and active ('rescue'). Oral short-acting opioid seems to be the most popular approach for BTP treatment, however, it is likely to be inadequate for a substantial proportion of patients as a result of the slow-onset of most available opioid preparations. Fentanyl buccal tablet (FBT) is a novel delivery system for fentanyl citrate. FBT utilizes OraVescent technology to improve bioavailability and speed of drug delivery. Recent studies have demonstrated superior pharmacokinetic profiles when compared with other available transmucosal opioids (OTFC), however, pharmacodynamic data are still somewhat limited.

Assessment of Dosing Frequency of Sustained-Release Opioid Preparations in Patients with Chronic Nonmalignant Pain

Many patients with moderate to severe chronic nonmalignant pain require dosing of long-acting opioids more frequently than recommended by the product's manufacturer. To accurately quantitate opioid dosing in clinical practice, daily dosing was prospectively assessed in pain clinic patients. A single-center, 30-day, prospective, observational cohort study, approved by the hospital IRB. Forty-one evaluable adult outpatients receiving treatment with long-acting opioids for moderate to severe chronic nonmalignant pain. The primary measure was the daily number of consumed doses of prescribed long-acting opioid. Rescue medication use, average daily pain intensity, and patient-reported adverse events were also recorded. The mean daily number of doses was 3.0 for oxycodone controlled release (CR), 2.9 for morphine CR, and 3.7 for methadone. For transdermal fentanyl, 50% of patients required dosing every 24-48 hours. Ninety-one percent of oxycodone CR-treated patients, 86% of morphine CR-treated patients, and 50% of fentanyl patch-treated patients required dosing more frequently than that recommended by the product's manufacturer. Patients who received oxycodone CR, morphine CR, and transdermal fentanyl required a mean of 2.9, 2.9, and 3.7 rescue doses per day, respectively. Many patients taking common long-acting opioids for chronic nonmalignant pain require dosing more frequently than recommended by product labeling, and take an additional 3-4 daily doses of rescue opioid, yet they continue to report moderate to severe pain. Newer opioid formulations that can provide sustained analgesia with convenient dosing are needed as well as a better understanding of the many additional factors that may influence opioid use patterns in patients with chronic pain.

Toward Evidence-Based Prescribing at End of Life: A Comparative Analysis of Sustained-Release Morphine, Oxycodone, and Transdermal Fentanyl, with Pain, Constipation, and Caregiver Interaction Outcomes in Hospice Patients

The primary goal of this investigation was to examine selected outcomes in hospice patients who are prescribed one of three sustained-release opioid preparations. The outcomes examined include: pain score, constipation severity, and ability of the patient to communicate with caregivers. This study included 12,000 terminally ill patients consecutively admitted to hospices and receiving pharmaceutical care services between the period of July 1 and December 31, 2002. We retrospectively examined prescribing patterns of sustained-release morphine, oxycodone, and transdermal fentanyl. We compared individual opioids on the aforementioned outcome markers, as well as patient gender, terminal diagnosis, and median length of stay. Patients prescribed a sustained-release opioid had similar average ratings of pain and constipation severity, regardless of the agent chosen. Patients prescribed transdermal fentanyl were reported to have more difficulty communicating with friends and family when compared with patients prescribed either morphine or oxycodone. On average, patients prescribed transdermal fentanyl had a shorter length of stay on hospice as compared with those receiving morphine or oxycodone. There was no difference in observed pain or constipation severity among patients prescribed sustained-release opioid preparations. Patients receiving fentanyl were likely to have been prescribed the medication due to advanced illness and associated dysphagia. Diminished ability to communicate with caregivers and a shorter hospice course would be consistent with this profile. Further investigation is warranted to examine the correlation between a patient's ability to interact with caregivers and pain control achieved.

Adverse effects and cognitive function among primary care patients taking opioids for chronic nonmalignant pain

Chronic opioid therapy is commonly prescribed for chronic nonmalignant pain. Few published data describe the adverse effects experienced by patients with chronic nonmalignant pain being treated by primary care physicians. A prevalence study was conducted on a sample of 1,009 patients (889 receiving chronic opioids) being treated by 235 primary care physicians. Standardized questionnaires and medical record reviews were used to assess rates of addiction, pain diagnosis and severity, opioid adverse effects, and mental health. The mean daily dose of opioids was 92 mg using a morphine-equivalent conversion. Side effects included constipation (40 percent), sleeping problems (25 percent), loss of appetite (23 percent), and sexual dysfunction (18 percent), with patients on daily opioids experiencing more side effects than subjects on intermittent medication. The Medical Outcomes Study Mental Health Inventory (MOS-MHI) cognitive functioning scale indicated poorer cognitive function in the overall sample of chronic pain patients as compared to a general clinical sample (delta x 95 percent CI = 9.28, 13.76). However, there were limited differences in MOS scores between chronic pain subjects on daily opioids vs. intermittent opioids vs. no prescription opioids. A regression model suggests that psychological measures and pain severity are more predictive of decrements in cognitive function than specific opioid preparations or daily opioid dose. Physicians should closely monitor patients for adverse effects and adequacy of pain control when using chronic opioid therapy for chronic pain treatment. Psychological health, an important predictor of cognitive dysfunction, is a particularly important measure to actively monitor and manage.

Open-Label Pilot Study of Testosterone Patch Therapy in Men With Opioid-Induced Androgen Deficiency

We conducted a 24-week open-label pilot study of testosterone (T) patch therapy in 23 men with opioid-induced androgen deficiency (OPIAD). The T dosage was 5 mg/day for the first 12 weeks and 7.5 mg/day for the second 12 weeks. Seven subjects discontinued prematurely: 4 for noncompliance, 2 for skin irritation and 1 for hepatitis C treatment. In the “completers” population (n = 16), mean (SD) free T levels (normal range 52 to 280 pg/mL) were 28.5 (18.6) pg/mL at baseline, 72.8 (29.6) pg/mL on 5 mg/day (P < .001 vs. baseline), and 120.2 (69.5) pg/mL on 7.5 mg/day (P < .001 vs. baseline and P < .01 vs. 5 mg/day). Total T, dihydrotestosterone, and estradiol showed parallel changes. Sex hormone–binding globulin levels were elevated at baseline and decreased modestly with treatment (P < .05 vs. baseline at 5 mg/day; P < .01 vs. baseline at 7.5 mg/day). Luteinizing hormone levels were in the low-normal range at baseline and suppressed markedly with treatment (P < .001 vs. baseline at both doses). Androgen deficiency symptoms (ADSQ), sexual function (Watts SFQ), mood (PGWB), depression (BDI-II), and hematocrit levels showed improvement during treatment, generally more so at the 7.5 mg/day dosage (P < .001 vs. baseline for most parameters). Pain scores (BPI-SF) decreased slightly on 7.5 mg/day (interference score: P < .05 vs. baseline and 5 mg/day); the use of opioids did not change appreciably. The testosterone patches were generally well tolerated. Perspective Long-acting opioid preparations suppress the hypothalamic-pituitary-gonadal axis in men and produce a symptomatic state of opioid-induced androgen deficiency (OPIAD). Testosterone patch therapy at a dose of 7.5 mg/day normalizes hormone levels and appears to improve a number of quality of life parameters (eg, sexual function, well-being, mood) in men with OPIAD.

The effects of immediate-release morphine on cognitive functioning in patients receiving chronic opioid therapy in palliative care

Morphine and other potent opioids are frequently used in palliative care and pain management. When sustained-release (SR) opioids do not provide adequate background analgesia, additional immediate-release (IR) opioid (e.g. short-acting morphine) may be required to alleviate breakthrough or episodic pain. Despite the frequent use of IR morphine on top of SR opioids, little is known about the effects of such treatment on patients' everyday cognitive functioning. This study therefore used a double-blind, placebo-controlled, cross-over design to assess cognitive functioning in 14 patients receiving palliative care. All patients were taking SR opioid preparations and required ≤2 doses of IR morphine/day. Performance on cognitive measures (as well as subjective measures of pain and mood) after a dose of IR morphine was compared with placebo. Patients experienced significantly more pain-reduction following IR morphine ( P=0.03), while other measures of subjective drug effects (e.g. sedation) were largely unaffected. Patients displayed anterograde memory impairment after IR morphine relative to placebo ( P=0.003). Intriguingly, patients also had significant ‘retrograde’ memory impairment: delayed recall of verbal information presented before IR morphine also declined ( P=0.024). In addition, IR morphine reduced performance on a complex tracking task (Reitan's trails B; P=0.03) whilst enhancing it on a simpler tracking task (Reitan's trails A; P=0.03). In conclusion, this study suggests that IR morphine, when taken on top of a SR opioid, produces transient anterograde and retrograde memory impairments and a decrement in two-target tracking. These impairments may impact negatively on patients' everyday functioning.

Perioperative management of acute pain in the opioid-dependent patient.

human rights. 2– 4 Noticeable shifts in attitude have occurred in recent years regarding the use of opioids for the treatment of benign and malignancy-related pain. Primary care physicians and pain specialists prescribe opioids to a greater number of patients and in doses appropriate to needs. 3–7 A variety of opioid analgesics and delivery systems have been introduced that have increased patient satisfaction, physician acceptance, and overall use. Concomitant with improvements in pain relief and quality of life, an increasing number of patients are affected by issues related to opioid tolerance and physical dependence. There have been only a small number of published reviews that address the treatment of acute pain in patients with substance abuse disorders, 3–5 and fewer have focused specifically on perioperative pain management in opioid-dependent patients. 6,7 This review outlines factors responsible for opioid tolerance, physical dependence, and addiction and provides perioperative analgesic dosing guidelines for this specialized subset of patients. Many patients who present for surgery and anesthesia may be opioid dependent or at least moderately tolerant to the therapeutic effects of opioid analgesics. 5–7 Causal factors underlying dependency include substance use disorder and, more commonly, legitimate use of opioid analgesics for treatment of chronic benign pain or malignancy-associated pain. Perioperative management of opioid-dependent patients poses a special challenge to primary caregivers, anesthesiologists, and pain specialists alike. This problem emanates from the often-conflicting needs to balance the rights of the patient on one hand and concerns of safety, diversion, and abuse on the

Opioids in non-cancer pain: Opioid Induced Androgen Deficiency in men (OPIAD): An estimate of the potential patient population in the U.S. and Canada

In men with chronic non-malignant pain, the use of long-acting opioid preparations of methadone, morphine sulfate, oxycodone and fentanyl frequently results in a syndrome of opioid induced androgen deficiency (OPIAD) (Daniell 2002). This syndrome is characterized by decreased serum levels of testosterone, decreased libido, erectile dysfunction, fatigue, depressed mood and hot flushes. Low testosterone levels decrease nociceptive threshold in animal models (Forman 1989, Pednekar 1995) and may also influence functional outcomes in men (Gruenewald 2003). Because of its clinical implications we have estimated the size of the potential patient population with OPIAD in the U.S. and Canada. We derived our U.S. estimate as follows: U.S. Population of Men age 18 and above: 101,000,000 (US Census 2000); 9–17% of U.S. Adults (age 18 and above) report having chronic non-malignant pain (CNMP) (multiple surveys); 3.4–39% of patients with CNMP are prescribed opioids, presumed to be of the long-acting type (Fanciullo et al. 2002; Potter et al. 2001); 74% of men prescribed long-acting opioids have subnormal testosterone levels (Daniell 2002). Based on these numbers, the estimated size of the potential OPIAD population in the US ranges from 229,000 to 5,000,000 men. Using the survey data of Moulin et al. 2002, the size of the OPIAD population in Canada is estimated to be approximately 154,000 men. In view of the rapidly increasing frequency with which opioids are being prescribed for chronic non-malignant pain (Joransen et al. 2000), we believe that our estimates are conservative. Nevertheless, the estimates presented here suggest that the potential patient population of men with OPIAD is sizeable, and that OPIAD is a syndrome that merits clinical evaluation and treatment.

Potent Analgesics Are More Expensive for Patients in Developing Countries

Opioids are the some of most important analgesic medications for the management of both moderate to severe pain and several are included on the World Health Organization (WHO) list of essential drugs. Opioid costs in developing countries have been reported to be higher than those in developed nations. This study documents retail prices and availability of several potent opioids in a number of developing and developed countries.Pain and Palliative Care specialists currently working in their countries were asked to collect data on the retail cost of a 30 day supply of 15 different opioid preparations in 5 developing and 7 developed countries. Data were analyzed to compare costs and costs as a percentage of gross national product (GNP) per capita per month.Opioid costs and availability varied widely in both developing and developed countries. Forty-five of 75 opioid preparations were available in developing countries (40% of medications studied were not available) and 76 of 105 preparations were available in the developed countries (28% not available). In US dollars, the median cost of opioids differed between developed and developing countries ($53 and $112, respectively) The median costs of all opioid preparations as a percentage of GNP per capita per month were 36% for developing and 3% for developed nations; the difference was statistically significant (p < 0.001). In developing countries, 23 of 45 (51%) of opioid dosage forms cost more than 30% of the monthly GNP per capita, versus only three of 76 (4%) in developed countries.The relative cost of opioids to income is higher in developing countries. Our data suggest that in developing countries opioid access for the majority of patients is likely to be limited by cost, and development of palliative care programs will require heavy or total subsidization of opioid costs.

Methadone and the hospice patient: prescribing trends in the home-care setting.

To identify frequency and utilization patterns of methadone by hospice patients in the home-care setting. All hospice patients admitted to a North American palliative care specialty pharmacy and dispensed methadone from November 1, 2001 to October 31, 2002 were analyzed. We also analyzed all hospice patients dispensed long-acting opioids during that same time period. A retrospective analysis of the pharmacy database was performed for patients dispensed methadone. Data was compared to the long acting opioid cohort to be able to identify any difference in terminal diagnoses present, and the presence of neuropathic pain in both groups. Methadone daily dosage was also analyzed during this study. Four hundred sixteen hospice patients were dispensed methadone over a twelve-month period of time. For comparison, 21,219 patients were prescribed a long-acting opioid preparation (sustained-release morphine, sustained-release oxycodone, or transdermal fentanyl). The most common terminal diagnosis for both groups was lung carcinoma. The distribution of terminal diagnoses was similar in both groups. The group prescribed methadone was found to have a higher incidence of neuropathic pain (30.5% of patients) when compared to the long-acting opioid group (16.9%). Most patients (61.3%) were prescribed daily methadone doses of 100 mg or less. Despite its potential clinical and economic benefits, methadone is not commonly prescribed for the hospice patient in the home-care setting. Clinicians may be more aware of the usefulness of methadone in the treatment of neuropathic pain.

PHYSIOLOGIC ABNORMALITIES AS BIOLOGIC MARKERS IN SEVERE, INTRACTABLE PAIN

It is recognized that biologic markers of severe, intractable pain (SIP) can help distinguish degrees of pain and assist in monitoring treatment effectiveness. Fifty (50.0%) adult ambulatory SIP patients, at the time of referral described their pain as constant, excruciating, produced a bed or house-bound state, and was uncontrolled by non-opioid medications and low dosages of the weak opioids, hydrocodone or codeine. Patients were treated with a long-acting opioid preparation consisting of methadone, oxycodone, morphine, or transdermal fentanyl in addition to a short-acting opioid for breakthrough pain. These patients were screened before treatment and after three months of opioid treatment by: (1) blood pressure; (2) pulse rate; (3) morning cortisol and pregnenolone serum concentrations; and (4) erythrocyte sedimentation rate (ESR). The percentage of patients with physiologic abnormalities before and after three months of treatment were as follows: (1) hypertension above 140/90 mm/Hg; 28 (56.0%) vrs 14 (28.0%); (2) tachycardia above 84/minute; 21 (42.0%) vrs 9 (18.0%); (3) elevated serum cortisol concentration; 12 (24.0%) vrs 2 (4.0%); (4) low serum cortisol serum concentration; 7 (14.0% vrs 1 (2.0%); (5) low pregnenolone serum concentration; 18 (36.0%) vrs 3 (6.0%); and (6) elevated ESR; 10 (20.0%) vrs 3 (6.0%) (p<.05). Mean blood pressure, pulse rate, ESR, and serum concentrations of cortisol and pregnenolone in patients who demonstrated a physiologic abnormality all positively and significantly (p<.05) altered these markers toward normal. This study indicates that some physiologic abnormalities, particularly those related to pituitary-adrenal over-stimulation with excess output of catecholamines and glucocorticoids, may serve as biologic markers which can help to identify SIP and monitor treatment effectiveness.

Australian management strategies for oral opioid use in non-malignant pain

Chronic non-cancer pain is a complex biopsychosocial phenomenon; as such it is unlikely that any one treatment modality will achieve relief. There is increasing availability of oral opioid preparations and an associated increased level of prescribing; consequently in 1997 the Australian Pain Society drew up some management strategies for their use. This paper reviews the principles of those strategies, stressing that oral opioids should not be used in isolation nor used to treat 'distress' often associated with chronic pain. The place of a trial of opioid and informed consent are discussed.

Developing Techniques and Strategies for the Management of Cancer Pain.

The past 20 years have seen a great surge of interest in understanding and treating pain. The introduction of sustained-release opioid delivery systems has tremendously advanced our ability to provide improved pain control. Parenteral opioid delivery systems, although available in many developed nations, remain expensive and cumbersome. New advances in parenteral sustained-release systems are currently in development. These advances include liposomal opioid preparations for intrathecal use, transcutaneous patient-controlled delivery, and implantable diffusion reservoirs. Even more exciting are new developments in tissue engineering that may allow the transplantation of human or animal cells, capable of producing natural analgesic substances, into the vicinity of the spinal cord.

The changing role of monitored anesthesia care in the ambulatory setting.

The changing role of monitored anesthesia care in the ambulatory setting.

Postoperative analgesia with parenteral opioids: Does continuous delivery utilizing a transdermal opioid preparation affect analgesic efficacy or patient safety?

Study Objectives: To compare, in patients who underwent major orthopedic surgical procedures, the efficacy of intravenous (IV) patient-controlled analgesia (PCA) with morphine combined with continuous administration of two doses of fentanyl or placebo via transdermal therapeutic system with fentanyl (TTSF) patches. Design: Randomized, double-blind, placebo-controlled study. Setting: University teaching hospital. Patients: 62 patients aged 18 to 65 years, presenting for elective orthopedic surgery and general anesthesia. Interventions: Patients were randomized to one of three groups: group 1 received two placebo patches; group 2 received a 20 cm 2 active patch delivering 50 μg/hr of fentanyl and a 30 cm 2 placebo patch; group 3 received a 30 cm 2 active patch delivering 75 μg/hr of fentanyl and a 20 cm 2 placebo patch. All patches were placed approximately two hours prior to induction of general anesthesia. General anesthesia was induced with thiopental, intubation facilitated by the use of vecuronium or pancuronium, and anesthesia was maintained with isoflurane in an oxygen/nitrous oxide mixture ( O 2 N 2O ). Following surgery, IV morphine was provided using IV PCA with 1.5 mg of morphine with a 6-minute lockout and a 4-hour maximum dosage of 30 mg. Measurements and Main Results: The time and dosage of morphine administered was recorded. Vital signs, pain intensity at rest, level of sedation, and arterial oxygen saturation (SpO 2) were measured at intervals throughout the 72-hour study period and at 6 and 12 hours following patch removal. The presence of side effects was noted. Visual analog pain scores throughout the 72 hours of the study were not significantly different among groups. Patients receiving active TTSF required less IV PCA morphine at all time intervals. However, total opioid consumption was comparable among groups. The incidence of side effects was similar in all groups. Conclusions: There is no significant advantage to the routine use of continuous transdermal opioid delivery in patients receiving TV PCA after major orthopedic surgery.

Local Analgesia with Opioid Drugs

These data suggest the presence of peripheral opioid receptors that are involved in the clinical perception of pain. This is a radical change in our traditional thinking of opioid pharmacology and pain management. Most clinicians have been taught that opioids work through the central nervous system. These new data depart from this traditionally held view of an exclusively central site of action. Further data, specifically, additional dose-response data with varying amounts of morphine, additional studies in pain syndromes other than knee arthroscopy, and the development and pharmacology of orally active opioid compounds that do not cross the central nervous system, are necessary to confirm and expand the present findings. The possibility of providing opioid pain relief free of central nervous system adverse effects is an exciting prospect. Additional studies of topical opioid preparations also would be of interest.

Electrophilic opioid ligands. Oxygen tethered alpha-methylene-gamma-lactone, acrylate, isothiocyanate, and epoxide derivatives of 6 beta-naltrexol.

O6-Ether derivatives of 6 beta-naltrexol in which the ether substituent includes various electrophilic groups have been synthesized in an effort to examine structure-activity requirements at the 6 beta-substituent for receptor affinity and irreversibility of binding in opioid receptor preparations. A series of tethered 6 beta-ethers having terminal epoxides, alpha-methylene-gamma-lactones, and an isothiocyanate group were prepared. The stereochemistry of the alpha-methylene-gamma-lactones was established by convergent synthesis of their reduction products from epoxides of known absolute stereochemistry. In general, the tested compounds showed comparable affinity and selectivity for the receptor subtypes. All were found with high affinity for mu-sites. The terminal epoxide ether diastereomers 8 and 9 were not bound irreversibly in the assay for total opioid receptors. The alpha-methylene-gamma-lactone diastereomers 10 and 11, and their O14-acetyl precursors 20 and 21, respectively, varied in their irreversible effects, but where noted these effects were mu-site selective. Methacrylate ether 7 and isothiocyanate ether 12 were bound irreversibly at both mu- and delta-sites.

Monoclonal anti-idiotypic antibodies to opioid receptors.

Two monoclonal anti-idiotypic antibodies (anti-Id-135 and anti-Id-14, both of the IgM class) which interact with the binding site of opioid receptors were generated. A monoclonal anti-beta-endorphin antibody (3-E7) which displays binding characteristics for opioid ligands similar to opioid receptors served as the antigen (Gramsch, C., Meo, T., Riethmüller, G., and Herz, A., (1983) J. Neurochem. 40, 1220-1226; Meo, T., Gramsch, C., Inan, R., Höllt, V., Weber, E., Herz, A., and Riethmüller, G. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 4048-4088) and the hybridomas obtained were screened for anti-idiotypic antibodies with Fab fragments of 3-E7. The anti-idiotypes were then screened for opioid binding to rat brain membrane receptors, yielding several positive clones two of which were more intensively studied. Both anti-idiotypic antibodies were about equally potent in displacing the mu- and delta-opioid receptor ligands [3H]dihydromorphine, 125I-labeled beta-endorphin, [D-Ala2, D-Leu5-3H]enkephalin and [3H]naloxone from rat brain membrane opioid receptors; no interaction was observed with the kappa-ligands [3H]ethylketazocine or [3H]bremazocine. The anti-idiotypic antibodies were able to precipitate [3H] diprenorphine binding sites from solubilized opioid receptor preparations. In addition, both antibodies showed opioid antagonistic properties as demonstrated by their abilities to block the inhibitory effect of [D-Ala2, D-Leu5-3H]enkephalin on prostaglandin E1-stimulated cAMP accumulation in NG 108-15 hybrid cells. Our findings demonstrate the successful generation of monoclonal antibodies interacting with membrane-bound and solubilized opioid receptors of the mu- and delta-type.

Differences of binding characteristics of non-selective opiates towards μ and δ receptor types

[ 3H]ET (etorphine), which is considered either as an “universal” ligand or a μ agonist, interacts with identical affinities K D = 0.33 – 0.38 nM to hybrid cells and rabbit cerebellum, pure δ and μ-enriched opioid receptor preparations, respectively. In rat brain tissue, [ 3H]ET binding is inhibited by DAGO (Tyr-D-Ala-Gly-(Me)-Phe-Gly-ol), a μ selective agonist, in a competitive manner without apparent modification of the maximal number of sites. Furthermore, even at a DAGO concentration (300 nM) which should be sufficient to block [ 3H]ET interaction with μ sites, no variation in the total capacity of the tritiated ligand is observed. In contrast, DTLET (Tyr-D-Thr-Gly-Phe-Leu-Thr), a δ-preferential agonist, blocks [ 3H]ET binding in rat brain at a concentration able to saturate δ-sites. At higher concentrations, where DTLET cross reacts with μ-sites, this ligand exhibits similar properties to those of DAGO. These data are very different from those obtained with [ 3H]EKC (ethylketocyclazocine), another “universal” ligand, the binding properties of which are easily explained by the occurence in rat brain tissue of independent sites exhibiting pharmacological profiles of μ, δ and κ sites. Our results underline the possible misinterpretation of binding data obtained by using [ 3H] etorphine as a non selective ligand.

Characterization of rabbit ear artery opioid receptors using a δ-selective agonist and antagonist

In order to characterize pre-junctional δ opioid receptors in the rabbit ear artery, the δ-selective agonist [D-Pen 2,D-Pen 5]enkephalin (DPDPE), and δ-selective antagonist, ICI 174,864, were used. The selectivity of these compounds for the δ receptor was confirmed using a standard opioid sensitive preparation, the mouse was deferens. Relative potencies of a series of opioid agonists were similar in the rabbit ear artery and the mouse vas deferens. Furthermore, K e values for IC 174,864 were not different in the two tissues. These findings demonstrate that δ opioid receptors in the rabbit ear artery and mouse vas deferens have similar properties.