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Biomedical subjects

K L Preston

Publications and source records attributed to K L Preston.

At least 109 records · Page 6Linked to original sources
PubMed1987

Comparative evaluation of morphine, pentazocine and ciramadol in postaddicts.

The subjective, physiological and behavioral effects of morphine, pentazocine and ciramadol, an opioid agonist/antagonist, were studied in adult male nondependent opioid abusers living on a clinical research ward. Fifteen subjects were assigned randomly to one of three groups. Each group received, by i.m. injection, placebo and three doses of one active drug, twice in randomized block order under double-blind conditions in 4.5-hr experimental sessions. Physiological measures did not differentiate between the three drugs. All three drugs decreased respiratory rate and pupil diameter and increased blood pressure. However, morphine, ciramadol and pentazocine produced different profiles on the subjective effect measures. All three drugs increased "liking," "good effects," "any effects" and "high" subjective effect scales. Pentazocine increased subjective "bad effects" scale scores and scales measuring dysphoria and sedation. Observers reported significant behavioral changes after administration of morphine and pentazocine, but not after ciramadol. Overall, the effects of morphine (7.5, 15 and 30 mg) and pentazocine (22.5, 45 and 90 mg) were dose-related. Although pentazocine produced increases in scales that indicated negative subjective effects, it also produced significant changes in most self-report measures that were increased by morphine, including liking and good effects scales. The effects of ciramadol were not dose-related, with all three doses (30, 60 and 120 mg) producing effects approximately equivalent to morphine 15 mg. Thus, ciramadol exhibited a ceiling effect typical of the opioid agonist/antagonist.

Adult↗
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

Diazepam and methadone blood levels following concurrent administration of diazepam and methadone.

Results of a previous study indicated that the opioid effects of methadone were enhanced by the concurrent administration of diazepam in methadone-maintained subjects. To determine whether a pharmacokinetic interaction might account for this methadone-diazepam interaction, the plasma levels of methadone, diazepam and diazepam metabolites were determined in blood samples collected during that study. Five adult male patients on methadone maintenance (50-60 mg/day) were administrated single doses of placebo, diazepam (20 and 40 mg), methadone (100%, 150% and 200% of the maintenance dose), and four diazepam-methadone dose combinations (20 and 40 mg diazepam in combination with 100% and 150% of the maintenance dose). The results showed that the concurrent administration of methadone and diazepam did not significantly change the time-course or areas under the plasma concentration-time curve of methadone, diazepam or N-desmethyl-diazepam compared to the levels following the administration of either drug alone. Thus, plasma drug level analysis does not indicate a pharmacokinetic interaction between diazepam and methadone.

Adult↗
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↗
PubMed1985

Long-term effects of repeated methylamphetamine administration on monoamine neurons in the rhesus monkey brain.

Previous studies indicate that the repeated administration of D-methylamphetamine (MA) produces a long-lasting depletion of dopamine (DA), norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) in various brain regions of a number of species. The objectives of the present study were: (1) to establish a short, subcutaneous injection regimen which would reliably produce the neuronal alterations; (2) to evaluate MA-induced NE depletions produced by this new regimen; and (3) to determine whether central MA-induced neuronal changes are reflected in changes in cerebrospinal fluid monoamine metabolite concentrations. It was observed that high doses of MA administered (s.c.) over a 2-week period to rhesus monkeys produced decreases in DA and 5-HT, but not NE levels, in various brain regions. The decrease in caudate DA levels was accompanied by a decrease in the number of DA uptake sites, a decrease in the level of homovanillic acid (HVA) and an increase in DA turnover. This decrease in brain DA was also accompanied by a decrease in the cerebrospinal fluid concentration of HVA.

Animals↗
PubMed1985

Methamphetamine, physostigmine, atropine and mecamylamine: effects on force lever performance.

Dose response functions for d-methamphetamine (MA), physostigmine, atropine, and mecamylamine on force lever performance (a measure of motor control) were determined in three rhesus monkeys. The rhesus monkeys were then treated with a repeated high dose regimen of MA, and the effects of the four drugs were redetermined. Following the completion of the behavioral studies, the monkeys were killed and brain monoamine concentrations were measured. It was found that each of the four drugs produced differential effects on force lever performance indices. Following the MA regimen, the MA-treated monkeys were less sensitive to the effects of MA on force lever performance but showed no change in sensitivity to any of the cholinergic agents. The monkeys were subsequently shown to have decreased brain dopamine and serotonin levels.

Animals↗
PubMed1985

Self-administration of clonidine, oxazepam, and hydromorphone by patients undergoing methadone detoxification.

The extent to which hydromorphone, clonidine, and oxazepam alleviate the symptoms of opioid withdrawal and the extent and pattern of self-administration of these drugs during methadone detoxification were examined within a residential laboratory in three groups of patients dependent on methadone. Six times over the course of detoxification, acute effects of orally administered placebo and a single active drug (hydromorphone HCl, 3 mg, clonidine HCl, 0.3 mg, or oxazepam, 30 mg, all given twice daily) were tested, followed by an opportunity for subjects to self-administer the drug and dose of their choice. Hydromorphone significantly decreased opioid withdrawal symptoms and was more preferred for self-administration than the placebo. Clonidine and oxazepam did not significantly decrease withdrawal symptoms, nor was either drug self-administered significantly more than placebo. Clonidine, however, did induce side effects.

Adult↗
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↗
PubMed1984

Effects of methamphetamine on atropine-induced conditioned gustatory avoidance.

The repeated administration of high doses of methamphetamine (MA) has been shown to cause monoaminergic damage in rhesus monkeys and rats. In view of the purported interaction between central cholinergic and monoaminergic systems, rhesus monkeys and rats previously exposed to high doses of MA were tested in conditioned gustatory avoidance studies with atropine (a muscarinic blocker) as the unconditioned stimulus. It was observed that both rhesus monkeys and rats previously exposed to high doses of MA exhibited less of an atropine-induced avoidance than control monkeys and rats. To control for the nonspecific effects of prior exposure to stimulants, an additional group of rats previously exposed to high doses of methylphenidate ( a stimulant shown to not cause catecholaminergic damage) was tested in the same paradigm. The methylphenidate treated rats showed no change in sensitivity to atropine in the conditioned gustatory avoidance paradigm as compared to control rats which indicated that prior exposure to the nonspecific effects of a stimulant without monoaminergic alterations does not alter the sensitivity of atropine's avoidance-inducing properties. The results of these experiments imply that atropine's avoidance-inducing properties may in part be mediated through the monoaminergic system.

Animals↗
PubMed1984

Diazepam and methadone interactions in methadone maintenance.

Survey study data and high rates of diazepam use/abuse in methadone maintenance suggest that acute administration of diazepam with daily methadone doses may enhance methadone effects. Acute subjective and physiologic effects of single oral doses of placebo, diazepam (20 and 40 mg), methadone (100%, 150%, and 200% of the maintenance dose), and four diazepam-methadone dose combinations (20 and 40 mg diazepam in combination with 100% and 150% of the maintenance dose) were assessed under double-blind conditions. The subjects were five adult male patients on methadone maintenance with histories of diazepam abuse who were receiving 50 to 60 mg methadone a day. Physiologic measures were continuously monitored for 30 min before and for 2 hr after dosing. Pupil diameter and subjective responses were measured 15 min before dosing and 15, 30, 45, 60, 90, and 120 min after dosing. Methadone induced dose-dependent increases in pupil constriction and scores on a subjective opioid effects rating scale, but diazepam had no significant effect on either. The combination of methadone at 150% of the maintenance dose with 40 mg diazepam induced increases in these measures greater than those induced by either drug dose alone. Drug combinations, however, were more frequently identified as being benzodiazepine/barbiturate-like than as methadone-like. Thus although the subjective effects of the drug combination are distinguishable from those of methadone alone, diazepam with methadone in methadone maintenance appears to increase some physiologic and subjective opioid effects that may be related to the relatively great use/abuse of diazepam in this population.

Administration, Oral↗
PubMed1982

A comparison of the central and peripheral effects of atropine on force lever performance.

The central and peripheral effects of atropine, a muscarinic antagonist, on motor control were tested in a force lever apparatus. Three rhesus monkeys were trained to extend their arms through a tube and press a manipulandum with between 25 and 40 grams of force for 3 continuous seconds. Responding was maintained by the delivery of 1.5 ml of water. Single injections of atropine sulfate or atropine methylnitrate (a quaternary derivative) of atropine which does not cross the blood brain barrier) were given 30 min prior to the session. Atropine sulfate disrupted force lever performance in a dose related fashion. Atropine methylnitrate had little or no effect on responding. The effects of atropine on motor control as measured in this procedure, therefore, appear to be centrally mediated.

Animals↗
PubMed1981

Conditioned gustatory avoidance induced by three cholinergic agents.

Conditioned gustatory avoidance of sweetened condensed milk was induced in rats by drugs which differentially affect the cholinergic nervous system. After baseline water intake during a 15 minute daily session was established, sweetened condensed milk was presented in place of water, followed 15 minutes later by an IP injection of saline, physostigmine (0.5 mg/kg), atropine (25 mg/kg) or mecamylamine (25 mg/kg). Three presentations of milk were given, alternating daily with a water presentation. Atropine, a muscarinic blocker, and mecamylamine, a nicotinic blocker, both produced a strong avoidance. Physostigmine, an indirect agonist, produced a less pronounced avoidance at the dose employed. This study indicates that cholinergic agonists and antagonists are capable of inducing conditioned gustatory avoidance.

Animals↗