levorphanol and Substance-Related-Disorders

Topics: Administration, Oral; Animals; Biotransformation; Body Weight; Codeine; Dealkylation; Dextropropoxyphene; Dogs; Guinea Pigs; Humans; Injections, Subcutaneous; Levorphanol; Meperidine; Methadyl Acetate; Morphine; Narcotics; Rabbits; Rats; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

Topics: Adult; Cranial Nerve Diseases; Female; Glossopharyngeal Nerve; Humans; Levorphanol; Neuralgia; Nurses; Professional Impairment; Substance-Related Disorders

Topics: Adult; Humans; Levorphanol; Male; Nonprescription Drugs; Substance-Related Disorders

Topics: Adult; Dextromethorphan; Humans; Levorphanol; Male; Substance-Related Disorders

A series of novel 2- and 3-acylmorphinans (8-14) was synthesized in our search for a potent analgesic agent with low addiction potential. The compounds were evaluated for antinociceptive potency and receptor binding affinity. Among these compounds, the levorotatory 3-acetyl-N-(cyclopropylmethyl)morphinan (12) was found to be an orally active analgesic, comparable in potency to morphine (1), yet only weakly able to substitute for morphine (1) in morphine-dependent rats.

Topics: Analgesia; Animals; Chemical Phenomena; Chemistry; Codeine; Humans; Levorphanol; Magnetic Resonance Spectroscopy; Morphinans; Morphine; Rats; Receptors, Opioid; Substance-Related Disorders

Prolyl-leucyl-glycinamide (PLG) at a low dose (10 ng/mouse) administered by an intracerebroventricular (i.c.v.) injection did not affect levorphanol analgesia, but PLG at higher doses (10 and 100 micrograms/mouse) and alpha-melanocyte-stimulating hormone (alpha-MSH) (10 ng/mouse) antagonized levorphanol analgesia. Development of levorphanol tolerance was facilitated by 10 ng/mouse of PLG, unaffected by 10 micrograms/mouse of PLG, but antagonized by 100 micrograms/mouse of PLG and 10 ng/mouse of alpha-MSH. The effect of PLG on levorphanol dependence was assessed by changes in body weight and temperature during naloxone-induced withdrawal. PLG (10 ng/mouse) facilitated the development of levorphanol dependence, but 10 micrograms/mouse of PLG had no effect. PLG (100 micrograms/mouse) antagonized development of levorphanol dependence. PLG at doses of 10 and 100 micrograms/mouse precipitated withdrawal in levorphanol-dependent mice. alpha-MSH (10 ng/mouse) antagonized development of levorphanol dependence as evidenced by an increase in the ED50 of naloxone required to induce withdrawal jumping. These results indicate that PLG and alpha-MSH affected levorphanol-induced analgesia, tolerance and dependence in a qualitatively similar manner to their effect on morphine-induced analgesia, tolerance and dependence.

Topics: Analgesia; Animals; Body Temperature; Body Weight; Dose-Response Relationship, Drug; Drug Tolerance; Humans; Levorphanol; Male; Melanocyte-Stimulating Hormones; Mice; MSH Release-Inhibiting Hormone; Naloxone; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Animals; Choice Behavior; Disease Models, Animal; Dopamine; Drinking Behavior; Female; Fenclonine; Humans; Hydroxydopamines; Levorphanol; Morphine Dependence; Norepinephrine; Rats; Rats, Inbred Strains; Self Administration; Serotonin; Substance-Related Disorders; Sucrose; Sweetening Agents

1 Physical dependence was produced in ilea from naive guinea-pigs by exposure of the tissue to different opiates for logarithmically-spaced periods of time (20-320 min). The responsiveness of the tissue to naloxone, as indicated by a strong contracture of the ileum, was enhanced in contrast to that found in intestines not exposed to opiates. 2 The dose-response curves to naloxone obtained in tissues individually exposed to different opiates showed that their relative potency in increasing sensitivity to naloxone was as follows: levorphan greater than morphine greater than Met-enkephalin greater than nalorphine greater than pentazocine. 3 The naloxone-induced response was dose-dependent and was directly related to the opiate concentration and length of exposure. 4 Dextrorphan the inactive isomer of levorphan, did not increase the responsiveness of the tissues to the narcotic antagonist, indicating that the phenomenon is stereospecific. 5 The naloxone-induced contraction in ilea exposed for 320 min to morphine (1 x 10(-6)M) was not prevented or suppressed by the administration of a large dose of morphine (1 x 10(-5)M) before or immediately after the naloxone challenge. 6 The evidence presented here shows that a phenomenon resembling in vivo opiate physical dependence can be acutely produced in vitro with pharmacological characteristics similar to other naloxone-induced abstinence effects.

Topics: Animals; Dose-Response Relationship, Drug; Enkephalin, Methionine; Enkephalins; Guinea Pigs; Humans; Ileum; In Vitro Techniques; Levorphanol; Male; Morphine; Nalorphine; Naloxone; Narcotics; Pentazocine; Substance-Related Disorders; Time Factors

Oral administration of levorphanol solution induces physical dependence in rats within a few days, as demonstrated by abstinence symptoms such as loss of body weight, sensitivity to touch and inversion of locomotor activity after withdrawal from the drug. In order to examine whether the physically dependent rats show an active drug-seeking behaviour they were given successively free choice between sweetened levorphanol solution (LSa) and two alternative drinking liquids -- sweetened tap water (WSa) and unadulterated water (W). In the case of LSa and W the rats chose LSa, but they preferred WSa to LSa. Another group of rats made dependent on unsweetened levorphanol solution (L) had the choice between L and W. They rejected L immediately.

Topics: Animals; Drinking Behavior; Female; Humans; Levorphanol; Male; Rats; Substance-Related Disorders; Sucrose; Taste

Changes in plasma corticosterone levels have been utilized as a sensitive and reliable indicator of opiate withdrawal. By using rats prepared with chronic indwelling i.v. catheters, drug injections and sequential blood sampling were accompanied in conscious undisturbed animals. Acute administration of levorphanol tartrate (LT) at 0.5, 1.0 or 2.0 mg/kg b.wt. caused an elevation in circulating corticosterone. With the lowest dose of LT, hormone levels returned to pretreatment values by 180 min. Naloxone hydrochloride (NX), 0.4 mg/kg, administered 3 hr after pretreatment with LT, 0.5 mg/kg, produced a significant elevation in plasma corticosterone. In contrast, animals pretreated with saline did not show the same increase in hormone levels after NX. NX, administered at several doses, along with LT, suppressed the plasma corticosterone increase which is normally observed when LT is given acutely. When NX is administered at sufficient dosage, along with LT pretreatment, the subsequent administration of the antagonist did not elicit the withdrawal response. These data indicate that a similar increase in plasma corticosterone, upon challenge with NX after a single dose of morphine, generalizes to other opiates. Blockade of the initial rise in plasma corticosterone and subsequent increase upon injection of the antagonist speak to the probability of the responses being related and opiate specific.

Topics: Animals; Corticosterone; Dextrorphan; Humans; Levorphanol; Male; Naloxone; Rats; Substance-Related Disorders

Topics: Alcohol Drinking; Animals; Animals, Newborn; Dextrorphan; Drug Interactions; Ethanol; Humans; Levorphanol; Male; Methadone; Methadyl Acetate; Mice; Mice, Inbred C57BL; Morphine; Naloxone; Naltrexone; Narcotic Antagonists; Narcotics; Rats; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

The injection of morphine sulfate into baby mice twice daily for 5 days increased their running reaponse to morphine when they were tested as adults. If treatment was completed before the mice were )5 days old there was no effect. Sensitization to morphine running was longer-lasting than either analgesic tolerance or tolerance to morphine running may be a form of denervation hypersensitivity that has several features in common with noise-induced sensitization to audiogenic seizures.

Topics: Age Factors; Animals; Animals, Newborn; Cocaine; Cycloheximide; Dextroamphetamine; Dextrorphan; Dose-Response Relationship, Drug; Drug Hypersensitivity; Drug Synergism; Female; Humans; Injections, Intraperitoneal; Injections, Subcutaneous; Levorphanol; Male; Mice; Mice, Inbred A; Mice, Inbred C57BL; Morphine; Motor Activity; Naloxone; Species Specificity; Substance-Related Disorders; Time Factors

Topics: Amphetamine; Apomorphine; Barbiturates; Chromatography, Thin Layer; Cocaine; Codeine; Cross Reactions; Cyclazocine; Dextromethorphan; Dextropropoxyphene; Evaluation Studies as Topic; Hemagglutination Inhibition Tests; Heroin; Humans; Hydromorphone; Levorphanol; Methadone; Methods; Microchemistry; Morphine; Nalorphine; Radioimmunoassay; Spectrometry, Fluorescence; Substance-Related Disorders; Time Factors; Tritium

Topics: Animals; Drug Tolerance; Humans; Injections, Intraperitoneal; Levorphanol; Male; Mice; Morphinans; Morphine; Narcotic Antagonists; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

Topics: Chemical Phenomena; Chemistry; Drug Antagonism; Humans; Levorphanol; Morphine; Nalorphine; Pentazocine; Substance-Related Disorders

Topics: Analgesics; Bridged-Ring Compounds; Chemical Phenomena; Chemistry; Cyclazocine; Humans; Levallorphan; Levorphanol; Morphinans; Morphine; Nalorphine; Naphthoquinones; Pentazocine; Substance-Related Disorders

Topics: Adrenal Glands; Animals; Body Weight; Brain; Drug Tolerance; Epinephrine; Female; Growth; Humans; Levorphanol; Methadone; Monoamine Oxidase Inhibitors; Morphine; Morphine Dependence; Norepinephrine; Organ Size; Rats; Stimulation, Chemical; Substance Withdrawal Syndrome; Substance-Related Disorders; Thebaine; Time Factors

Topics: Aged; Amitriptyline; Chlorpromazine; Codeine; Dextromoramide; Humans; Levorphanol; Male; Pain; Substance-Related Disorders