Biomedical subjects
Publications and source records attributed to P Irwin.
The quantitative EEG profile of a putative antihistaminic drug, terfenadine, was determined in a crossover comparison with diphenhydramine in normal male volunteers. Terfenadine failed to elicit the characteristic EEG or behavioral effects of sedative antihistaminics, and was distinguishable from diphenhydramine. The EEG profile confirmed the lack of CNS effect observed in preclinical and clinical trials.
Among the newer psychoactive compounds, clozapine is classified by some authors as an antipsychotic compound, but it exhibits differences in pharmacology and clinical effects that clearly distinguish it from established antipsychotic compounds. It represents an anomaly in the EEG classification scheme as well. In normal volunteers and in psychotic patients, it elicits EEG effects that are more like those of sedative thymoleptic antidepressants than the established antipsychotic compounds. It is probable that the antipsychotic activity reported by some observers reflected the sedative qualities of the compound and not a prototypic antipsychotic activity. Further testing in other psychiatric populations, particularly patients with depressive illnesses, is warranted.
The electroencephalographic (EEG) and behavioral effects of oral doses of phenytoin from 100 mg to 1 g in normal male volunteers were measured. The electroencephalogram exhibited decreases in power in the slow frequencies and increases in the fast frequencies, accompanied by an increase in mean frequency. These changes are similar to those seen with psychostimulants. They occurred at average plasma levels of 8 micrograms/ml and above. The time course and the intensity of EEG effects parallel plasma levels. Drug-related EEG changes were bilaterally symmetric. EEG changes at plasma levels of 8--12 micrograms/ml were not associated with behavioral toxic signs. These findings suggest that future psychiatric studies of phenytoin as a psychostimulant should include monitoring for plasma levels, with a minimum of 8 micrograms/ml as a guide to clinical efficacy.
1. The clinical efficacy of mianserin, a tetracyclic compound, was compared with imipramine and placebo in 47 hospitalized depressed patients. 2. The clinical ratings showed that the three treatment groups improved equivalently during hospitalization. 3. Plasma levels of mianserin correlated with changes in the Hamilton Rating Scale for depression, total score and two of its factors (anxiety/somatization, and retardation) and the item 'late insomnia'. 4. Drowsiness was a more frequent side-effect among mianserin patients on day 4; no other side-effect distinguished the treatments. 5. No relationship between MHPG levels and treatment or treatment outcome were observed.
1. Electroencephalogram (EEG) recordings and blood level assessments were included in a clinical comparison of the effects of mianserin (GB-94), imipramine and placebo in depressed, hospitalized patients during a 3-week observation period. 2. Temporal changes in behavioural ratings were observed, but these failed to be distinguished among the active drugs and placebo. EEG measures also showed temporal changes, but these also failed to distinguish among the drug conditions, except at 2 h after administration of the first dose. 3. Plasma levels of mianserin were obtained with EEG recordings in a temporal relationship to the behavioural assessments. There were no correlations between the changes in EEG variables and plasma levels of mianserin, or between EEG and behavioural variables, except on acute administration. The lack of discrimination for the EEG variables may be related to the quality of the EEG recordings and the poor control of the temporal relationships of behavioural assessments to EEG recording and drug dosing.
A pharmacokinetic analysis of a new antidepressant drug, mianserin (ORG GB-94), was undertaken in 4 male volunteers, each of whom received 15 mg mianserin on two occasions. Plasma levels peak at 2 h with a median level of 11.0 ng/ml, a median beta-phase half-life of 10.0 h, and a median apparent volume of distribution of 3.3 X 10(3) 1. EEG profile analysis shows mianserin to increase frequencies below 6 Hz, decrease those from 7.5 to 15 Hz, and increase frequencies above 18 Hz, a pattern similar to amitriptyline. Peak EEG effects range from 2 to 5 h with a pattern of measured changes that parallels plasma levels with varying latency. Decreases in vigilance measures and in critical flicker-fusion frequency show a similar time course. Mianserin is a putative thymoleptic on EEG profile analysis with high cerebral penetrance.
The relationships between attitudes toward homosexuality and sociodemographic and attitudinal variables were explored, using the data from a nationwide opinion survey in the United States. Individuals who were willing to grant such rights to homosexuals as teaching in college, speaking in a local community, and removing a book from a local library written by a homosexual and favorable to homosexuality, tended to be well educated, young, Jewish or nonreligious, from urban areas, raised in the Northeast or Pacific states, and willing to provide freedom of expression to people with nonconformist political ideas. "Erotophobia," which was not related closely to the rights issue, was associated with moral judgments about homosexual acts.
Effects of the heptapeptide ACTH4-10 (Org OI-63) on EEG, some memory tests, and behavior were examined in 12 normal male volunteers under 30 years of age. An intravenous dose of 60 mg was compared to placebo in a Latin square design. EEG was recorded for 2 h after administration of ACTH4-10 or placebo and was quantified by power spectral density analysis. Drug differences were tested by analyses of variance and covariance. No statistical drug effect was seen on the EEG or behavioral measures. Of the psychological tests, only the digit span test showed a decrease in number of errors with ACTH4-10 (p less than or equal to o.05). These results are consistent with previous studies and suggest that an intravenous bolus of ACTH4-10 has a limited effect on the brain function tested.
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