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Biomedical subjects

H B McNamee

Publications and source records attributed to H B McNamee.

At least 19 recordsLinked to original sources

D-1 dopaminergic and beta-adrenergic stimulation of adenylate cyclase in a clone derived from the human astrocytoma cell line G-CCM.

Clones have been isolated from the human astrocytoma cell line G-CCM. Homogenates of clone D384 contain an adenylate cyclase that is stimulated by 3,4-dihydroxyphenylethylamine (dopamine), noradrenaline, and isoprenaline with Ka apparent values of 4, 56, and 2.7 microM, respectively. The Ka apparent value for dopamine was increased by the D-1 antagonist cis-flupenthixol, 25 and 100 nM, to 23 and 190 microM, respectively, but was unaffected by propranolol (1 microM). Noradrenaline stimulation of adenylate cyclase was only partially inhibited by either propranolol (10 microM) or cis-flupenthixol (1 microM). Propranolol (10 microM), but not cis-flupenthixol (1 microM), prevented stimulation by isoprenaline. The stimulation of adenylate cyclase by dopamine and noradrenaline remained unchanged in the presence of phentolamine (1 microM) and sulpiride (1 microM). These results suggest that clone D384 contains both D-1 dopaminergic and beta-adrenergic receptors coupled to adenylate cyclase. Dopamine stimulates D384 adenylate cyclase through D-1 receptors, isoprenaline via beta-receptors, and noradrenaline through both receptors.

Adenylyl Cyclases↗

Cannabis and the peripheral nervous system.

The possible ill-effects of cannabis on the peripheral nervous system were examined in 27 male subjects with respect to their motor and sensory nerve conduction. They were classified by their previous cannabis use into casual and heavy users. The nerve conduction studies were done after a baseline period of five days and then repeated after a three-week period during which the subjects could acquire and smoke standardized cannabis cigarettes. The casual users smoked a mean of 54-3 and the heavy users a mean of 109-5 cigarettes during the smoking period. No deterioration of peripheral nerve function could be demonstrated.

Adult↗

Behavioral and social effects of heroin self-administration and withdrawal.

Behavioral and social reactions to intravenously administered heroin were studied during a 33-day experimental addiction cycle. Three groups of four subject volunteers were allowed to self-administer heroin for a ten-day period as part of a longer study of oplate antagonists. Data relevant to sleep patterns, energy expenditure, social interaction, and other observable behaviors were collected during hourly observations. Comparison of behavioral differences before and after drug administration indicated few significant acute reactions. Reactions to long-term heroin self-administration were most pronounced in the areas of sleep behavior and social interaction. Subjects tended to sleep less, especially during the initial period of acquisition, and to withdraw more from social contact. No changes were noted in energy expenditure during waking hours. The results were interpreted in terms of physiological tolerance, central nervous system arousal, and sleep deprivation.

Adult↗

A behavioral paradigm for the evaluation of narcotic antagonists.

We have developed an experimental paradigm for the behavioral evaluation of narcotic antagonists. The study specifically examined the heroin-seeking behavior of hard-core narcotic addicts on a research ward under blocked and unblocked conditions. Each patient served as his own control. A long-term follow-up program in the community, with aftercare services, was utilized to determine the relationship between behavior observed on the research ward and behavior that occurred in the community. While preliminary one-month follow-up data offered some cause for an optimistic view of narcotic antagonist treatment, behavioral data observed on the research ward raised serious doubts about the possibility of extinguishing heroin self-administration with antagonists. The behavioral data were not consistent with laboratory descriptions of extinction. Rather, the data suggested that narcotic antagonist programs should emphasize the development of contingencies for the reinforcement of narcotic antagonist self-administration to ensure an opiate-free state, instead of focusing on an extinction approach.

Adult↗

Psychopathology and mood during heroin use: acute vs chronic effects.

In the context of evaluating the effects of a narcotic antagonist on opiate acquisition, 14 detoxified addicts self-administered increasing doses of unblocked heroin intravenously over a ten-day period. Early in the addiction cycle, subjects experienced tension relief and euphoria but this was followed shortly by a shift in the direction of increasing dysphoria and psychopathology. Nonetheless, individual injections of the drug continued to induce brief episodes of positive mood, an effect enhanced by frequent injection. Heroin self-administration was sharply reduced when subjects were blocked with naltrexone, a narcotic antagonist, and the negative effects observed during unblocked drug use were not observed.

Acute Disease↗

Analysis and modification of opiate reinforcement.

The authors describe a research protocol for the evaluation of narcotic antagonists which examines the heroin-seeking behavior of hard-core heroin addicts on a research ward under blocked and unblocked conditions. Each patient served as his own control. This paper serves as an introduction to a series of papers which follow dealing with behavioral, psychiatric, and aftercare results. It describes detailed methods and preliminary results for the first 21 subjects admitted to the study. More specific results are reported in the papers that follow.

Adult↗

Opiate antagonists and the modification of heroin self-administration behavior in man: an experimental study.

The heroin self-administration behavior of 8 inpatient heroin addicts was examined for 10 days under blocked (i.e., following ingestion of narcotic antagonists--naloxone or naltrexone) and unblocked (no antagonist) conditions. In the unblocked state, subjects injected all the available heroin, but they ceased heroin use almost completely following antagonist administration. Possible explanations for these results are discussed along with their implications for treatment.

Adult↗

Psychopathology, craving, and mood during heroin acquisition: an experimental study.

Six detoxified addict volunteers were allowed to self-administer intravenous heroin on an essentially self-determined schedule. Two periods of heroin acquisition were compared: an unmodified cycle in which patients could become intoxicated and a later cycle in which the effects of heroin were blocked with a narcotic antagonist. In the unblocked condition, patients initially experienced an increase in positive mood, but with chronic administration there was a significant rise in psychopathology and the development of a generalized dysphoric state. Similar changes did not occur when the same patients took heroin while blocked with a narcotic antagonist. Drug craving rose dramatically when "unblocked" heroin was available, but gradually fell during methadone detoxification. Following treatment with a narcotic antagonist, the presence of heroin failed to elicit any sustained rise in craving and drug taking was dramatically reduced.

Adult↗

Fenmetozole in acute alcholol intoxication in man.

Forty healthy adult male volunteers were studied to determine the efficacy of fenmetozole to antagonize the effects of acute alcholol intoxication. Twenty subjects receive placebo and 20 fenmetozole in dosage of 100 mg and 200 mg in a double-blind paradigm. Pretreatment with fenmetozole failed to antogonize or attenuate cognitive, perceptual, motor and affective changes associated with acute alchol intoxication.

Adult↗