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PubMedDate not supplied

Pharmacological actions of levallorphan allyl bromide (CM 32191), a new peripheral narcotic antagonist.

A dissociation of the effects of the newly synthesized quaternary ammonium narcotic antagonist, levallorphan allyl bromide (CM 32191) on morphine-induced analgesia and constipation in the mouse is reported. CM 32191 behaved as a pure morphine antagonist on the "in vitro" preparation of longitudinal muscle of guinea-pig ileum and antagonized dose-dependently the peripherally mediated morphine constipation (ID50:15.6 mg/kg) without significantly affecting morphine analgesia (ID50: greater than 80 mg/kg). Its peripheral selectivity was greater than that of another quaternary ammonium compound, N-methyl naloxone. It is proposed as a useful pharmacological tool to differentiate the peripherally mediated from the centrally mediated effects of opioids.

Animals↗
PubMed1983

Levallorphan methyl iodide (SR 58002), a potent narcotic antagonist with peripheral selectivity superior to that of other quaternary compounds.

The peripheral selectivity of the newer quaternary narcotic antagonist levallorphan methyl iodide (SR 58002) was found superior in mice to those of the previously available compounds N-allyl levallorphan (CM 32191), N-methyl nalorphine (MNph) and N-methyl naloxone (MNx). SR 58002 and MNph were the most potent (ID50, mg/kg s.c., 3.6 and 3.7) in preventing constipation by s.c. morphine (charcoal meal). Antinociception (hot-plate) of s.c. morphine was completely prevented by MNx, MNph and CM 32191 (ID50, mg/kg s.c., 1.6, 8.6 and 15.2) but only partially antagonized by 30 mg/kg s.c. SR 58002. Constipation elicited centrally by intracerebroventricular (i.c.v.) morphine was prevented by either s.c. MNx or MNph but not by SR 58002 or CM 32191, up to 60 mg/kg.

Animals↗
PubMed1993

Narcotic receptor blockade and its effect on the analgesic response to placebo and ibuprofen after oral surgery.

The purpose of this study was to evaluate the contribution of endogenous opiates to the analgesic response after treatment with placebo, codeine, and ibuprofen after oral surgery. Eighty-one patients undergoing complicated dental extractions were pretreated with either a placebo or the narcotic antagonist naltrexone 50 mg, 30 minutes before surgery. After surgery, patients self administered one of three possible postsurgical medications, which included placebo, codeine 60 mg, and ibuprofen 400 mg, when their pain reached a moderate or severe intensity. The study was double-blind with the three postsurgical treatments being randomly allocated within each presurgical treatment block. Pain intensity, pain relief, pain half gone, and overall evaluations were assessed for up to 6 hours. Ibuprofen was significantly more efficacious (p < .05) than codeine or placebo for most analgesic measures. The administration of naltrexone before surgery reduced the analgesic response to both placebo and codeine. Pretreatment with naltrexone did not diminish the peak analgesic response to ibuprofen, but surprisingly prolonged (p < .05) the duration of its action. The results suggest that a blockade of endogenous opiates by naltrexone diminished the placebo response, but that naltrexone may prolong ibuprofen analgesia by some unknown mechanism.

Adult↗
PubMed1994

LTP in hippocampal CA1 of urethane-narcotized rats requires stronger tetanization parameters.

Rats with chronically implanted electrodes in the hippocampal CA1 region were tested in their capacity to express and maintain long-term potentiation (LTP) of the population spike (PS) or of the field excitatory postsynaptic potential (fEPSP). Two different states were compared: a) freely moving animals; b) urethane-anesthetized animals (1 g/kg, IP). We found that a short, high-frequency tetanus (six bursts of 15 pulses; 200 Hz; double-pulse width; interburst interval 10 s) increased PS amplitudes and fEPSP slopes up to 300% in response to test stimuli in double-pulse width; interburst interval 10 s) increased PS amplitudes and fEPSP slopes up to 300% in response to test stimuli in the awake rat. The PS amplitude slowly decreased in time, returning to baseline levels 4 h post-tetanically, whereas the fEPSP slope remained at higher values for 24 h. Urethane injection reduced the fEPSP slope and abolished the PS to normal test pulses. We thus increased the strength of the test stimuli until we again recorded magnitudes of PSs and fEPSPs comparable to those in the awake animal. In conjunction with these stronger stimuli, tetanus-induced LTP was elicited that for the PS was increased in magnitude and prolonged in duration compared to the untreated control group. Although, stronger tetanic stimuli were applied to the narcotized fEPSP group too, no difference was found compared to controls. These results suggest that urethane narcosis influences the sensitivity of CA1 neurons to express LTP. Stronger stimulation was required to induce and maintain a long-lasting potentiation of the fEPSP slope and PS amplitude.

Animals↗
PubMed1990

Clinical significance of platelet-associated immunoglobulins in narcotic addicts with human immunodeficiency virus infection.

Increased amounts of platelet-associated immunoglobulin G (PAIgG) have been reported in human immunodeficiency virus (HIV)-infected patients with thrombocytopenia. We have prospectively investigated PAIgG in 21 asymptomatic (group A; CDC stages IIA-IIB) and 9 symptomatic (group B: CDC stages IIIB-IV) HIV-infected narcotic addicts. In both groups only two subjects presented with a decreased platelet count. By competitive ELISA, we found a 1.8- and 2.3-fold greater total PAIgG (PAIgGtot) as measured on platelet lysates in group A and B, respectively; surface-bound IgG (PAIgGsurf) as measured on intact platelets was 2.5- and 3.0-fold greater in groups A and B, respectively, as compared to 36 controls. The ratio between PAIgGtot and PAIgGsurf was lower in HIV-infected addicts when compared to controls (P less than 0.05). This indicates that platelets from HIV-infected subjects not only have increased surface and internal pools of PAIgG, but also present with a distribution between these two pools that differs from that of normal platelets. In addition, levels of circulating immune complexes (CIC) were abnormally raised in 17/21 (81%) subjects of group A in 6/9 (66%) subjects of group B.

Adult↗
PubMed1979

Possible non-narcotic component to action of opiate peptides on tonic immobility.

Chickens were tested in a tonic immobility paradigm after a single intraperitoneal injection of either 0.0, 0.1, 1.0, 10.0; 100.0, or 1000.0 microgram/kg of the potent opiate analog, (D-Ala2, F5Phe4)-Met-enkephalin-NH2. An inverted-U relationship was obtained, with 100 microgram/kg being the most effective in prolonging immobility. This dose was used in subsequent studies involving pretreatment with naloxone or diluent followed by treatment with diluent, (D-Ala2, F5Phe4)-Met-enkephalin-NH2 (a strong opiate), or (D-Phe4)-Met-enkephalin (a weak opiate). The results indicated that although naloxone had mixed effects in attenuating the duration of tonic immobility, even the analog with negligible opiate activity reliably potentiated the response. Therefore, a component of the effect of opiate peptides on tonic immobility could be due to a non-narcotic action.

Animals↗
PubMed1979

Evidence for a mutagenic effect of the narcotic antagonist, naltrexone, in germ cells of Drosophila.

The narcotic antagonist, Naltrexone, was tested for mutagenicity in Drosophila. The frequency of sex-linked recessive lethals at a non-toxic dose of 10 mg/ml was 0.43% (42 lethals in 9697 X-chromosomes tested) and 0.16% (19/11536) in the controls. The difference is statistically significant (P less than 0.001). Results from large-scale experiments testing for chromosome breakage and nondisjunction were negative.

Animals↗
PubMed1984

Relative cataleptic potency of narcotic analgesics, including 3,6-dibutanoylmorphine and 6-monoacetylmorphine.

Dose-response curves were constructed for duration of significant catalepsy in male Sprague-Dawley rats following i.p. administration of four established and two novel narcotic analgesics. The relative potency of the six drugs was levorphanol greater than monacetylmorphine greater than diacetylmorphine greater than dibutanoylmorphine greater than morphine greater than meperidine. Cataleptic potency correlated with analgesic potency for morphine, diacetylmorphine, and dibutanoylmorphine but not for monoacetylmorphine.

Animals↗
PubMed1981

Actions of kappa, sigma and partial mu narcotic receptor agonists on rat brain acetylcholine turnover.

Cholinergic neurons which possess mu and delta receptors and/or which are regulated by neurons possessing these receptors, do not appear to have kappa receptors. Only at doses far exceeding (16--32 x) the analgesic ED50 of the prototype kappa antagonist ethylketazocine is acetylcholine turnover depressed in the cortex and hippocampus. This suggests that such activity may involve occupation of mu and/or delta receptors at high doses. The lack of activity of the sigma agonist SKF 10047 also indicates a possible absence of sigma receptors on cholinergic neurons. The partial mu antagonist buprenorphine was found to be a unique narcotic agent in that it behaved as a classical mu agonist at low doses, but as an antagonist at high doses.

Acetylcholine↗
PubMed1981

Propoxyphene napsylate maintenance treatment for narcotic dependence: a non-methadone model.

One hundred and seventy eight heroin addicts entered propoxyphene napsylate (PN) maintenance. Patients attended a general medical clinic twice each week and took home a three- to four-day supply of PN, to be taken in doses of 300 to 400 mg three or four times per day. Over a 21-month period, subjects entered and re-entered PN treatment 266 times (1.5 times per patient) and remained in treatment a mean of 10.6 weeks. When compared with a group of methadone maintenance patients, similar characteristics in employment and heroin use were found. The ability to take PN, attend a clinic less often than daily and discontinue and re-enter treatment on a discretionary basis is a preferred treatment approach for some narcotic addicts.

Adult↗
PubMedDate not supplied

The relationship between hepatitis B surface antigen and antibody and continued drug use in narcotic dependency: a randomized controlled study.

Hepatitis B surface antigen (HBsAg) and antibody (antiHBs) were determined in 556 narcotic addicts entering a randomized prospective study of alcoholism in patients on methadone maintenance. Only 37% of patients were either negative for HBsAg or without detectable titers of antiHBs. No difference in reactivity existed between alcoholic as compared to nonalcoholic patients and the use of street heroin as compared to use of methadone upon entry to the study. At least a one year follow-up was obtained in 229 (41%) patients with 25 of 88 (28%) patients initially without titers to antiHBs developing detectable titers. No relationship existed between development of antiHBs titers and elevation of liver function tests or the subsequent use of parenteral heroin. These findings suggest that the development of titers to antiHBs in persons on methadone maintenance should not be used as an indication of parenteral drug use.

Alanine Transaminase↗
PubMed1983

Significance of tattooes in narcotic abusers.

Social aspects of tattooed compared to non-tattooed narcotic addicts attending a methadone maintenance programme were investigated. It was found that those who were tattooed reported greater current social instability and a more deprived background compared to those without tattooes. None of the tattooes specifically identified the subjects as belonging to the drug scene nor could the age at which the subject was first tattooed be used to predict subsequent drug abuse. The presence of tattooes was unrelated to the current dose of methadone and to the duration of attendance on the methadone programme.

Adult↗
PubMed1977

The narcotic-dependent mother: fetal and neonatal consequences.

During the years 1971--1974, 230 infants born to drug-dependent women and 33 infants born to ex-addicts were studied. Heroin abuse declined while methadone usage increased during those years. Compared to heroin abuse, methadone maintenance treatment during pregnancy was associated with more consistent prenatal care, more normal fetal growth and reduced fetal mortality. Meconium staining of amniotic fluid was increased in the heroin and heroin-methadone groups; this was not associated, however, with an increase in meconium aspiration or a reduction in Apgar scores. Of special note was the equally severe intrauterine growth retardation of infants of former heroin addicts who were free of narcotic use during pregnancy. Neonatal withdrawal from methadone appeared to be more severe than from heroin, as judged by amount of medication required to control symptoms and duration of treatment. In all groups, central nervous system signs were the most common manifestations of withdrawal. Severity of withdrawal did not correlate with late pregnancy maternal methadone dosage. Neonatal seizures occurred in 1.5% of the heroin group and 10% of the methadone group. Discharge of an infant to a parent rather than to an alternate care-taker was more likely if the mother was enrolled in a methadone treatment program. Methadone maintenance programs appear to offer significant therapeutic benefits, balancing the untoward effects of the drug on the newborn infant.

Adult↗
PubMed1984

Non-narcotic orally effective, centrally acting analgesic from an Ayurvedic drug.

Embelin, a p-quinone, is derived from Embelia ribes Burm. The analgesic effect of potassium embelate has been studied in rats and mice. The test drug was found to be effective by oral, i.m. and i.c.v. routes and the results compared well with morphine. Although potassium embelate acts centrally to produce analgesia, its effect is not antagonized by naloxone indicating a different central site of action. There is no precipitation of abstinence syndrome as observed with morphine. Peripheral site of action of the drug is ruled out as it lacks any demonstrable anti-inflammatory action. It can be concluded that high oral efficacy and non-narcotic properties of the test drug make it more acceptable than morphine. In addition, lack of any adverse effects, high therapeutic index and absence of abstinence syndrome confers a long term safety on potassium embelate for use as an analgesic.

Acetates↗
PubMedDate not supplied

Emergency department analgesia without narcotics for adults with acute sickle cell pain crisis: case reports and review of crisis management.

Vaso-occlusive crises are one of the most debilitating features of sickle cell disease. There appears to be no standardization of care for adults with pain crisis, and some commonly utilized regimens, such as those employing intramuscular meperidine, are pharmacologically unsound. Parenteral narcotic use may be associated with respiratory compromise acutely and with dependence over the long term, but nonopioid preparations are often unsatisfactory in relieving pain. We have recently enjoyed success with a combination of a parenteral nonsteroidal anti-inflammatory medication and an oral tricyclic antidepressant. We report four representative cases and review the salient points of the management of pain crisis in adult patients in the emergency department.

Acute Disease↗
PubMed1986

Narcotic and other drug use: a spectrum.

Zinberg and Lewis foresaw developments in the substance abuse field in particular and in human services in general with the development of a "Spectrum of a Difficult Medical Problem." We believe this spectrum has far reaching implications and value for researchers, theoreticians, planners and practitioners currently in the substance abuse field both in conceptualizing drug involvement with its diversity of potential concerns, as well as planning treatment for drug involved clients. The application of a spectrum need not be limited to the category of drugs known as narcotics; this concept can also be applied to involvement with drugs from other categories, e.g., stimulants, sedative/hypnotics, hallucinogens, etc.

History, 20th Century↗
PubMed1987

Studies on the effects of the narcotic alkaloids, cocaine, morphine, and codeine on nonenzymatic lipid peroxidation in rat brain mitochondria.

This paper presents evidence of studies on the effects of the narcotic alkaloids, cocaine hydrochloride, morphine sulfate, and codeine phosphate, on nonenzymatic lipid peroxidation in rat brain mitochondria. These organelles abound in polyunsaturated fatty acids and are thus susceptible to oxidative attack. Lipid peroxidation was indexed mainly by assaying the extent of malonaldehyle (MDA) production and also the formation of fluorescent products in the course of the reaction. We found that morphine sulfate lowered fluorescence while the other two alkaloids showed no effect on lipid peroxidation in the absence of the inducers, 1.0 mM ascorbic acid or 0.1 mM ferrous sulfate. The apparent antioxidative nature of morphine sulfate was also observed in its effects on induced and noninduced MDA production, both cocaine hydrochloride and codeine phosphate stimulated MDA production by about 20% in the absence of any inducers. This paper also attempts to draw a structure-activity relationship for the antioxidative action of opium alkaloids, which we postulated to be due to the chelating capability of the alkaloid molecule.

Alkaloids↗
PubMedDate not supplied

Efficacy of ketorolac in lieu of narcotics in the operative management of laparoscopic surgery for morbid obesity.

BACKGROUND: Prompt recovery of protective airway reflexes, freedom from pain, ability to cooperate with respiratory physical therapy, early ambulation and discharge from the postanesthesia care unit (PACU), coupled with a stable intraoperative environment have been desired goals of anesthesia management of morbidly obese patients. We used ketorolac in lieu of narcotics toward this goal and present our subjective and objective data in this study. METHODS: A total of 50 morbidly obese patients undergoing laparoscopic gastric bypass surgery were randomly assigned to 2 groups of 25 each. Group I received intravenous ketorolac perioperatively, which was continued 24 hours postoperatively. Group II received remifentanyl intraoperatively as a part of balanced anesthesia. Intraoperative hemodynamic stability was assessed based on blood pressure, pulse rate, and bispectral index score values. Postoperative pain intensity using a visual analogue scale, as well as the presence of nausea, vomiting, hypotension, or respiratory depression, were also recorded. RESULTS: Postoperative side effects, including pain, nausea, and vomiting; requirements for analgesics and antiemetic medications in the PACU; and the time spent in the PACU varied significantly between the 2 groups. Continued administration of ketorolac during the first 24 hours postoperatively led to improved patient satisfaction and more enthusiastic participation in respiratory physical therapy. CONCLUSIONS: Perioperative use of intravenous ketorolac up to 24 hours after laparoscopic gastric bypass surgery for morbid obesity helps provide a more stable intraoperative environment, earlier discharge from the PACU, and better outcome in this subset of patients.

Adolescent↗