Arnold B. Davidson

Validity and Reliability of the Observer??s: Assessment of Alertness/Sedation Scale

The Observers Assessment of Alertness/Sedation (OAA/S) Scale was developed to measure the level of alertness in subjects who are sedated. This scale was tested in 18 subjects in a three-period crossover study to assess its reliability and its criterion, behavioral, and construct validity. After receiving either placebo or a titrated dose of midazolam to produce light or heavy sedation, each subject was administered two sedation scales (OAA/S Scale and a Visual Analogue Scale) and two performances tests (Digit Symbol Substitution Test and Serial Sevens Subtraction). Two raters individually evaluated the subjects level of alertness on each of the two sedation scales. The results obtained on the OAA/S Scale were reliable and valid as measured by high correlations between the two raters and high correlations between the OAA/S Scale and two of the three standard tests used in this study. The OAA/S Scale was sensitive to the level of midazolam administered; all pairwise comparisons were significant (p < 0.05) for all three treatment levels at both test periods.

Moclobemide in social phobia: A controlled dose-response trial

Although the monoamine oxidase inhibitor phenelzine has proven efficacious in social phobia, the risk of hypertensive crises has reduced its acceptability. The reversible monoamine oxidase inhibitor moclobemide has less potential for such reactions, but its efficacy in this disorder remains unproven. A double-blind, placebo-controlled study was undertaken to assess the efficacy and safety of fixed doses of moclobemide. After a 1-week placebo run-in, subjects with social phobia were randomly assigned to placebo or one of five doses (75 mg, 150 mg, 300 mg, 600 mg, or 900 mg daily) of moclobemide for 12 weeks. Although a trend toward greater efficacy of higher doses of moclobemide was observed at 8 weeks, no differences in response to various doses of the drug and placebo were observed at 12 weeks. At 12 weeks, 35% of subjects on 900 mg of moclobemide and 33% of those on placebo were at least much improved. Moclobemide was well tolerated, insomnia being the only dose-related adverse event observed with the drug. In this dose-response trial, moclobemide did not demonstrate efficacy at 12 weeks. Some other controlled studies have found moclobemide and brofaromine, another reversible monoamine oxidase inhibitor, efficacious in social phobia. Possible reasons for inconsistent findings are discussed.

Pharmacological effects of Ro 22-1319: A new antipsychotic agent

Ro 22-1319, a novel pyrroloisoquinoline compound, was identified as a potential antipsychotic agent in a rat discrete avoidance procedure that is highly specific for such agents. Results in this test are highly correlated with the clinical potency of all types of antipsychotic agents. The avoidance-blocking potency of Ro 22-1319 (0.7 mg/kg) in this procedure approached that of haloperidol (0.4 mg/kg) and was 7- and 12-times greater than that of chlorpromazine and clozapine, respectively. Ro 22-1319 exhibited similar high potency in other rat and monkey avoidance procedures, rat motor activity, and antagonism of apomorphine emesis in dogs. High potency and antipsychotic-like activity have been demonstrated in monkey EEG and in a in vivo 3H-spiroperidol binding assay. Although studies of amphetamine antagonism in rats indicate antidopaminergic activity at nigrostriatal sites, Ro 22-1319 exhibited relatively weaker cataleptogenic and antistereotypic activity than haloperidol, and had minimal activity in a rat chronic stereotypy model of receptor supersensitivity. This profile suggests that Ro 22-1319 is an efficacious antipsychotic compound, almost as potent as haloperidol, with fewer or less intense extrapyramidal effects and low potential for tardive dyskinesia.

Pharmacological Protection Against Memory Retrieval Deficits as a Method of Discovering New Therapeutic Agents

The material in this chapter represents one component of a more global approach to the discovery of drugs to treat a variety of cognitive disorders. The broader plan, which is described in greater detail elsewhere (1), is based on a pragmatic behavioral approach to the search for agents to treat cognitive disease states that may range from attention deficit disorders (or hyperkinesis) and dyslexia in children to forget-fulness and Alzheimer’s disease in the aged. This overall broad-based approach requires examination of many types of behaviors representing a number of processes and is functional in nature. Although such a behavioral program can exist on its own, it is usually employed in conjunction with one or more specific biochemical or chemical hypotheses.

Effects of chlorpromazine on continuous avoidance behavior in mice

Previous reports have indicated that self-trained appetitive operant schedules of reinforcement can be acquired readily by mice using an apparatus which detects head movement responses. Using a similar apparatus, suitably modified, the utility of this methodology has been extended to an operant schedule of reinforcement in which behavior is maintained by an aversive shock stimulus. As previously demonstrated with various other CNS active drugs in the appetitive mouse procedures, the effects of chlorpromazine in the mouse continuous avoidance procedure described here were similar to those obtained in analogous standard rat procedures. These results increase the opportunities for experimenters to avail themselves of the advantages offered by the use of mice, rather than rats, in operant behavioral pharmacology.