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PubMed1997

Comparing the subjective, psychomotor and physiological effects of intravenous nalbuphine and morphine in healthy volunteers.

The purposes of this study were to characterize the subjective, psychomotor and physiological effects of nalbuphine in healthy non-drug abusing volunteers and to compare and contrast the effects of equianalgesic doses of nalbuphine and morphine. Subjects (12 males, 4 females) without histories of opiate dependence were injected in an upper extremity vein with 0, 2.5, 5.0 or 10 mg/70 kg nalbuphine, or with 10 mg/70 kg morphine, using a randomized, double-blind, crossover design. The 10-mg doses of nalbuphine and morphine are considered equianalgesic and are doses commonly given for relief of postoperative pain. Subjective effects of nalbuphine included increased scores on the Pentobarbital-Chlorpromazine-Alcohol Group scale and the Lysergic Acid Diethylamide scale of the Addiction Research Center Inventory; increased adjective checklist ratings of "nodding," "numb" and "sweating"; increased visual analog scale ratings of "coasting or spaced out," "high" and "sleepy" and increased "feel drug effect" and drug-liking ratings. Ten milligrams of nalbuphine had subjective effects similar, and similar in magnitude, to those of 10 mg of morphine. Nalbuphine produced exophoria and impairment on the Digit Symbol Substitution Test in a dose-related fashion. Ten milligrams of morphine produced exophoria but did not affect performance on the Digit Symbol Substitution Test. Both nalbuphine and morphine induced miosis and decreases in respiration rate. The results of the present study demonstrate that 2.5 to 10 mg nalbuphine had orderly, dose-related effects on subjective, psychomotor and physiological variables. The results also indicate that 10 mg of nalbuphine produces a profile of subjective, psychomotor and physiological effects similar to that of an equianalgesic dose of morphine (10 mg). The similarity in profiles between drugs at this dose is consistent with both infrahuman studies, which suggests that nalbuphine is a mu agonist, and studies with nondependent opioid abusers, in which relatively low doses of nalbuphine (such as 10 mg) produce morphine-like effects.

Adult↗
PubMed1997

The recanting of earlier reported drug use by young adults.

One approach to determining the validity of self-reported drug use measures is to examine the extent of logically inconsistent responses over time. Because lifetime use logically should never decline, the rate of subsequent recanting of earlier reported lifetime use provides relevant evidence on validity. In this chapter, recanting rates are examined in nationally representative samples of high school seniors (18-year-olds) surveyed in the Monitoring the Future study as they are followed up on seven occasions through age 32. For the illegal drugs examined (marijuana, cocaine, and lysergic acid diethylamide (LSD)), recanting rates prove to be quite modest, but for the psychotherapeutic drugs, they were more substantial, possibly because of their greater definitional ambiguity. In general, there were no large individual differences in recanting rates as a function of sex, household composition, community size, or education level. Consistent with previous work, minorities (particularly African Americans) had somewhat higher rates of recanting on the illegal drugs. So did respondents in certain occupations, namely, the military and police/firefighting. In general, however, the evidence is quite good for validity of self-reported (by mail) lifetime use of the illegal drugs in young adulthood.

Adolescent↗
PubMedDate not supplied

Involvement of 5-hydroxytryptamine 2A (5-HT2A) receptors in the mediation of the discriminative stimulus properties of (+/-)DOI in rats.

Rats were trained to discriminate between the 5-HT2A/2C receptor agonist (+/-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(+/-)DOI, 0.35 mg/kg] and saline using a two-lever drug discrimination procedure; afterwards, the effects of different 5-HT agonists and antagonists on the discriminative stimulus properties induced by (+/-)DOI were studied. In substitution tests, D-lysergic acid diethylamide (LSD, 0.02 and 0.04 mg/kg) and quipazine (0.5, 1.5 and 3 mg/kg), 5-HT2A/2C agonists, evoked dose-related responses to the (+/-)DOI-appropriate lever, while the non-selective 5-HT agonist 1-(3-chlorophenyl)piperazine (m-CPP, 0.1, 0.5 and 1 mg/kg), which has the highest binding affinity for 5-HT2C receptors, failed to show substitution. In antagonist studies, the discriminative stimulus effect of (+/-)DOI was completely antagonized by ketanserin (0.5 mg/kg) and cyproheptadine (0.5 mg/kg), preferential 5-HT2A receptor antagonists, and partially by the 5-HT2A/2C receptor antagonist mesulergine (0.25, 0.5 and 1.0 mg/kg) and the 5-HT2A/D2 antagonist spiperone (0.025, 0.05 and 0.1 mg/kg). The above data suggest that the discriminative stimulus effects of (+/-)DOI are predominantly mediated by 5-HT2A receptors.

Amphetamines↗
PubMed1998

Cloning and functional expression of an Aplysia 5-HT receptor negatively coupled to adenylate cyclase.

Serotonin (5-HT) is involved in the control of various behaviors in Aplysia californica, including reproduction, feeding, locomotion, circadian rhythm, synaptic plasticity, and synaptic growth. The large variety of functions of 5-HT is mediated by different receptor subtypes that are coupled to different second-messenger systems. Here, we report the cloning of a cDNA coding for an Aplysia G-protein-coupled 5-HT receptor (5-HTap1). Its deduced amino acid sequence resembles those of the 5-HT1 receptor subfamily. When expressed in stable cell lines, 5-HTap1 exhibits high-affinity binding for the serotonergic radioligand [N-methyl-3H]lysergic acid diethylamide. This binding is competed by several 5-HT agonists and antagonists, and the pharmacological profile of inhibition has some similarities with those of 5-HT1 and 5-HT7 receptors. Application of 5-HT or its agonists 5-carboxamidotryptamine maleate and (+/-)-8-hydroxy-2-(di-n-propyl-amino) tetralin hydrobromide on cells transformed with 5-HTap1 produced a dose-dependent inhibition of forskolin-stimulated cAMP accumulation. 5-HTap1 is thus negatively coupled to adenylate cyclase. The production of antiserum against the 5-HTap1 receptor allowed us to examine its expression in animal tissues. The receptor protein is detected in every tissue examined, although it seems only weakly expressed in some samples. The receptor is also found in every ganglia of the nervous system, both in the sheath and in the neurons. 5-HTap1 mRNA is absent from the sheath, indicating that the protein observed there is probably located on the nerve terminals.

Adenylyl Cyclase Inhibitors↗
PubMed1998

Comparing the subjective, psychomotor and physiological effects of intravenous pentazocine and morphine in normal volunteers.

The purposes of this study were to characterize the subjective, psychomotor and physiological effects of pentazocine in non-drug-abusing volunteers and to compare and contrast the effects of pentazocine with those of morphine. Sixteen subjects without histories of opiate dependence were injected in an upper extremity vein with 0, 7.5, 15 or 30 mg/70 kg pentazocine or 10 mg/70 kg morphine, using a randomized, double-blind, crossover design. Pentazocine increased scores on the pentobarbital-chlorpromazine-alcohol group and lysergic acid diethylamide scales and decreased scores on the benzedrine group scale of the Addiction Research Center Inventory, increased adjective checklist ratings of "nodding," "sweating" and "turning of stomach" and increased visual analog scale ratings of "difficulty concentrating," "drunk" and "having unpleasant bodily sensations." Pentazocine (30 mg) had a greater propensity to increase ratings associated with dysphoria than did 10 mg of morphine. Pentazocine produced impairment on four measures of psychomotor performance. Ten milligrams of morphine produced minimal psychomotor impairment. Both pentazocine and morphine induced miosis, but 10 mg of morphine had a greater magnitude of effect than 30 mg of pentazocine. The results of the present study demonstrate that 7.5 to 30 mg of pentazocine had orderly, dose-related effects on subjective, psychomotor and physiological variables. Further, a clinically relevant dose of pentazocine, 30 mg, produced a greater magnitude of dysphoric subjective effects than did 10 mg of morphine, which is consistent with the literature reporting that pentazocine has a greater likelihood of inducing psychotomimesis than do other opioids.

Adult↗
PubMedDate not supplied

3-Dimensional anatomic relationship of serotonergic and muscarinic receptor binding in the pontine reticular formation of the human infant brainstem.

Cholinergic and serotonergic neurons of the rostral pontine reticular formation have been implicated by animal studies in the modulation of sleep and waking. To define better the spatial relationships between muscarinic and serotonergic receptor binding in the rostral human brainstem, we used 3-dimensional computer reconstructions of serial autoradiographs generated with radioligands to muscarinic and serotonergic receptors. Receptor binding was assessed in a series of 9 human infants, and 3-dimensional reconstructions were performed in a representative infant at 53 postconceptional weeks. The computer reconstructions demonstrated a 3-dimensional distinct pattern in the rostral pontine reticular formation, with high (3H)lysergic acid diethylamide binding to serotonin receptors in the median raphe nucleus flanked by paramedian bands of high (3H)quinuclidinyl benzilate binding to muscarinic cholinergic receptors in the medial nucleus pontis oralis. Based upon comparisons to animal data, we suggest that the muscarinic-serotonergic pattern of receptor binding in the rostral pontine reticular formation represents part of the neurochemical organization of the circuitry involved in the modulation of rapid eye movement (REM) sleep in humans.

Autoradiography↗
PubMed1996

The drug-use situation in the Czech Republic.

This article reports on a rapid assessment conducted in the Czech Republic during the second half of 1995. The main aim of the assessment was to describe patterns of illicit drug use, particularly in the capital, Prague. A Rapid Assessment Board was established to oversee the study, and both secondary and original data were collected from a range of sources. Illicit drug use was found to have increased throughout the country in the preceding five years, with amphetamines being the most popular substance. Polydrug use is common. There has been an increase in the use of the so-called "dance drugs", especially lysergic acid diethylamide (LSD), among younger people, and heroin, especially in the main urban areas. Injecting is on the increase, too. There is an urgent need to expand both fixed-site and community-based services.

Adolescent↗