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Biomedical subjects

D R Jasinski

Publications and source records attributed to D R Jasinski.

At least 55 records · Page 3Linked to original sources
PubMed1987

An analysis of naltrexone precipitated abstinence in morphine-dependent chronic spinal dogs.

Graded doses of naltrexone (0.31, 1.125, 5.0, 20.0 and 80.0 micrograms/kg) were administered to five beagle-type dogs dependent on increasingly large stabilization doses of morphine (0.5, 1.0, 2.0, 4.0, 8.0, 16.0 and 24.0 mg/kg/day) and the intensity of precipitated abstinence (PAS) was determined by a previously developed scoring system. A complete crossover design was executed with all dogs receiving all doses of both naltrexone and morphine. The data were analyzed using a two-way analysis of variance (dogs and treatments). Treatment variance was partitioned into a regression and residual component. A mathematical model for relating the intensity of abstinence (PAS) to the concentrations of morphine and naltrexone was developed using the law of mass action and assuming that the degree of morphine physical dependence is related directly to the number of mu receptors occupied by morphine and the intensity of PAS is proportional to the number of receptors from which morphine is displaced by the antagonist. Using the mathematical model the deviations of the observed values from the calculated values were minimized using an iterative curve-fitting procedure which varied the values of the dissociation constants of morphine (KA) and naltrexone (KB) and the activity coefficient for morphine (alpha). The analysis of variance showed that the treatment effect was significant and that the regression accounted for most of this variance. The values which provided the best fit were: KA, 1.58 mg/kg; KB, 0.95 microgram/kg; and alpha, 245.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Investigation of the abuse liability of buspirone in alcohol-dependent patients.

By use of the Addiction Research Center Inventory, the Amphetamine Self-Rating Scale, the Single-Dose Questionnaire, and selected physiologic measures (blood pressure, pulse and respiratory rates, oral temperature, and pupil diameter), the abuse liability of buspirone (10, 20, and 40 mg) was compared with that of diazepam (10 and 20 mg) and placebo in 19 subjects who were hospitalized for the treatment of alcohol dependency. Each treatment was given as a single dose at intervals of at least three days according to a double-blind, six-period, crossover Latin square design. Neither buspirone nor diazepam had any effect on blood pressure, pulse and respiratory rates, or body temperature. A small, transient pupillary constriction was evident in the 20- and 40-mg buspirone groups, but it dissipated within two hours after dosing. Both buspirone and diazepam had only a small stimulating effect on appetite. On the Pentobarbital-Chlorpromazine-Alcohol Group and Sedation subscales of the Addiction Research Center Inventory, the 40-mg dose of buspirone yielded effects suggestive of a mild sedative-type drug. Only the 20-mg dose produced a significant effect on the Euphoria scale. Diazepam appeared to be more active as a sedative-hypnotic type of drug, by virtue of its effects on both the Amphetamine and Euphoria subscales and its greater effects on the Morphine-Benzedrine Group, Pentobarbital-Chlorpromazine-Alcohol Group, and Sedation subscales, suggesting euphoria. Not only does the lack of effect of buspirone on the Amphetamine and Morphine-Benzedrine Group subscales indicate lack of a euphorigenic property, but the score on the Lysergic Acid Diethylamide subscale, especially in the 40-mg group, suggests a dysphorigenic property at high doses. On the Amphetamine Self-Rating Scale, buspirone and diazepam affected only the sleep factor and only the 40-mg buspirone dose was distinguishable from placebo. On the Single-Dose Questionnaire, both buspirone and diazepam tended to be rated more as sedative-type drugs, but buspirone was generally less well liked than diazepam. Overall, the results, which suggest a lack of euphoria and the presence of dysphoria at high doses, indicate that buspirone has only limited, if any, abuse liability.

Administration, Oral↗
PubMed1986

Evaluation of mixtures of morphine and d-amphetamine for subjective and physiological effects.

Combinations of morphine and d-amphetamine have been shown to be more effective in relieving pathological and experimental pain with fewer side effects than morphine alone. Subjective, physiological and behavioral effects of the combination were assessed in the present study to determine whether the abuse liability of the combination might also be enhanced. Single intramuscular doses of morphine and d-amphetamine alone and in combination were tested under double-blind conditions in 10 adult, male, non-dependent substance abusers. Morphine and amphetamine alone increased scores on subjective effect measures including the Morphine-Benzedrine Group (MBG) (euphoria) and liking scales. In general, the combination produced greater euphoria than that produced by either drug alone. In contrast, many physiological effects of the drugs were mutually antagonized. Thus, the combination of morphine and d-amphetamine has a greater potential to be abused because of the additive euphoria and a lessening of side effects.

Body Temperature↗
PubMed1986

Evaluation of tilidine for morphine-like subjective effects and euphoria.

Tilidine is an opioid analgesic that has been abused predominantly by the oral route. Studies of parenterally administered tilidine in animals did not clearly indicate a dependence potential of the morphine type. In this study we examined the abuse potential of orally and parenterally administered tilidine in humans. Both orally and intramuscularly given tilidine produced miosis and morphine-like subjective effects in non-dependent subjects. Oral tilidine was 1/8-1/10 as potent and intramuscular tilidine was 1/22 as potent as parenteral morphine in producing morphine-like subjective and miotic effects. Intramuscular tilidine suppressed and did not precipitate signs of abstinence in morphine-dependent subjects. However, intramuscularly given tilidine produced toxic effects not seen with morphine. Meperidine, codeine and d-propoxyphene produced morphine-like subjective and miotic effects, but also produced toxic effects at the highest doses tested. The results suggest that tilidine has a potential to be abused, that this potential is less than that of parenteral morphine and that tilidine is more likely to be abused orally than by the intramuscular route.

Administration, Oral↗
PubMed1986

Comparison of intravenously administered methadone, morphine and heroin.

Data from previously reported studies suggest that methadone may be more euphorigenic than other morphine-like drugs. To determine whether methadone is more potent in producing euphoria relative to its other opiate-like effects, single doses of intravenously administered methadone, morphine, heroin and placebo were compared in non-dependent post-addict volunteers. Morphine-like physiologic, subjective and behavioral effects were measured periodically for 24 h after drug administration. Under the conditions of the experiment methadone produced a profile of effects which was indistinguishable from that of morphine and heroin. Only the time course of miosis, which was longer lasting following methadone, differentiated among the three compounds. The relative potencies of methadone, morphine and heroin for the initial 5 h of effect were constant over all opiate-like effects, including measures of euphoria. Thus, methadone was not a selective euphoriant.

Adult↗
PubMed1986

The clinical pharmacology of pentazocine and tripelennamine (T's and Blues).

The incidence of abuse of pentazocine and tripelennamine (T's and Blues) suggests that the mixture has greater abuse potential than does either agent alone. Pentazocine (40 and 80 mg), tripelennamine (50 and 100 mg), alone and in combination, and placebo were administered in random order to volunteering experienced drug users. Pentazocine alone and tripelennamine alone were identified as opioids and produced euphoria. The large dose of pentazocine produced sedation and dysphoria. Pentazocine and tripelennamine both raised blood pressure; pentazocine constricted pupils, tripelennamine did not. The addition of 50 mg of tripelennamine increased the euphoric effects of pentazocine and attenuated the dysphoric effects seen at higher doses. Adding 100 mg of tripelennamine did not appreciably increase further the euphoric effects and did not alter the dysphoric effects of high doses of pentazocine. The combination significantly increased the systolic and diastolic blood pressure, and the increase was at least additive. In combination, pupillary constriction was slightly antagonized. These studies suggest that the antihistamine tripelennamine has abuse potential, and that in combination with pentazocine, the euphoric effects of the opioid are enhanced and its dysphoric properties attenuated.

Arousal↗
PubMed1985

Clonidine in morphine withdrawal. Differential effects on signs and symptoms.

Reports of an antiwithdrawal effect for clonidine hydrochloride in acute opioid withdrawal are inconsonant with experimental findings that other nonopioids are ineffective. In the present investigation the antiwithdrawal effects of clonidine, morphine sulfate, and placebo were compared in volunteer addicts whose dependence was maintained by 15 mg of morphine sulfate given subcutaneously four times daily. Clonidine was effective but had a differential effect on the signs and symptoms of morphine abstinence. Compared with morphine, clonidine was more effective in suppressing autonomic signs of abstinence but less effective in reducing subject-reported symptoms and discomfort. It is concluded that the perception of the clinical usefulness of clonidine depends on whether objective measures or subjects' reports are treated.

Clonidine↗
PubMed1985

Assessment of dezocine for morphine-like subjective effects and miosis.

Dezocine is an analgesic soon to be marketed in the United States. In this study we examined the abuse potential of dezocine. Subjective and miotic effects of single subcutaneous doses of dezocine, morphine, and placebo were assessed under double-blind conditions in 10 adult male nondependent drug abusers. Dezocine and morphine were equipotent in inducing a constellation of effects typical of opioid agonists, including miosis and increases in opioid signs and symptoms, liking, and euphoria. Both drugs were consistently identified by subjects as being "dope" (opiates). Thus the profile of effects of single doses of dezocine indicate that the drug has the potential to be abused. However, the agonist-antagonist activities of dezocine demonstrated by others suggest that its abuse potential is less than that of morphine.

Analgesics, Opioid↗
PubMed1985

Abuse liability and pharmacodynamic characteristics of intravenous and inhaled nicotine.

The potential role of nicotine in tobacco dependence was investigated using the strategies of abuse liability assessment. Eight male volunteer cigarette smokers with histories of drug abuse resided on a research ward for the duration of the study. Each subject was tested with three doses of i.v. nicotine (0.75, 1.5 and 3.0 mg/10-sec infusion) and placebo each test day, and with three doses of inhaled nicotine, in the form of research cigarette smoke (0.4, 1.4 and 2.9 mg estimated yield) and placebo (sham-smoking), given on alternate test days. Each subject was tested on 4 days with both routes of administration, according to identical experimental protocols. Physiologic, subjective and observer data were collected at intervals ranging from 15 sec to 10 min beginning 10 min before drug administration and continuing for 30 min after administration. Both i.v. and inhaled nicotine produced dose-related increases in heart rate and blood pressure, and i.v. nicotine produced a transient bradycardia in four subjects during the first 30 sec after drug administration. Skin temperature was decreased by nicotine and pupil diameter was not consistently changed. Ratings of drug dose "strength" and drug "liking" were directly related to dose level whereas "desire to smoke cigarettes" was inversely related. Scores on the Morphine-Benzedrine Group (or Euphoria) scale of the Addiction Research Center Inventory were elevated by nicotine, and i.v. doses were identified frequently as cocaine. Signs and symptoms were similar for nicotine across the two routes of administration and included coughing, dizziness, nausea and relaxed feelings. Nicotine shared the pharmacologic profile of prototypic drugs of abuse. The study supports the hypothesis that the role of nicotine in tobacco dependence is equivalent to the role of other psychoactive drugs in substance abuse, e.g., to the role of cocaine in coca leaf use.

Adult↗
PubMed1984

Electroencephalographic and behavioral correlates of buprenorphine administration.

Male subjects on methadone maintenance who were residing in a research ward were switched to buprenorphine for 45 days. Physiologic measures, behavioral and subjective ratings of mood states, and an electroencephalogram (EEG) were obtained daily. Distinct changes in EEG activity paralleled physiologic and behavioral effects during the transition to buprenorphine. Similar physiologic effects and a reversal of EEG effects occurred when saline solution was substituted for buprenorphine. It is concluded that, consistent with its classification as a partial opiate agonist, buprenorphine may not substitute fully for methadone.

Adult↗
PubMed1983

Cigarette smokers self-administer intravenous nicotine.

Human volunteers who smoked cigarettes were given the opportunity to press a lever that resulted in intravenous injections of saline or nicotine. Nicotine injections were taken in orderly patterns that were related to unit dose, whereas patterns of saline injections varied widely. Furthermore, the volunteers reported that nicotine produced subjective effects similar to those produced by administration of abuse drugs such as morphine or cocaine.

Adult↗
PubMed1983

Abuse potential of zomepirac.

Zomepirac sodium, a nonsteroidal anti-inflammatory analgesic, was compared to morphine sulfate and placebo in an abuse liability study in a postaddiction population. Morphine (15 and 30 mg), but not zomepirac (400 and 800 mg), induced pupillary constriction and characteristic morphinelike subjective effects. The 800-mg dose of zomepirac was discriminated but was not euphorigenic. This study indicates that zomepirac is not likely to be abused.

Blood Pressure↗