Comparative Neurologic Effects of Diazepam and Suriclone, a Cyclopyrrolone Anxiolytic

1 In a double-blind, placebo-controlled, cross-over study, acute pharmacokinetic, neurophysiological and psychotropic effects of suriclone, a new cyclopyrrolone derivative, were investigated and compared with alprazolam. 2 Fifteen normal young volunteers received randomized oral single doses of placebo, 0.1, 0.2 and 0.4 mg suriclone as well as 1 mg alprazolam as reference compound. Investigations were carried out before and 1, 2, 4, 6 and 8 h after drug administration. 3 Pharmacokinetic investigations by radioimmunoassay showed a dose-dependent fast rise of plasma concentrations with a peak at 1 h and a rapid decline thereafter. Both the Cmax and the AUC values exhibited a linear relationship to dose.4 EEG brain mapping demonstrated significant CNS effects of both compounds, characteristic for tranquillizers (increase of beta, decrease of alpha and increase of delta activity; attenuation of total power and acceleration of the centroid, i.e. centre of gravity frequency). When compared with alprazolam, suriclone exerted less sedative effects. 5 Time-efficacy calculations showed the pharmacodynamic peak effect of suriclone from the 2nd to the 4th hour, and of alprazolam in the 1st hour. Dose-efficacy calculations showed that the most pronounced CNS changes occurred after 1 mg alprazolam, followed by 0.4, 0.2 and 0.1 mg suriclone. 6 Psychometric investigations demonstrated no significant effects after the two lower doses of suriclone, while 0.4 mg and 1 mg alprazolam induced a decrement both in noopsychic and thymopsychic variables seen after higher doses of anxiolytic sedatives. Psychophysiology (critical fficker fusion, pupillometry, and skin conductance measures) pulse rate, systolic and diastolic blood pressure remained unchanged. 7 Psychophysiology (critical fficker fusion, pupillometry and skin conductance measures)showed differential dose-dependent effects. Pulse rate, systolic and diastolic blood pressure remained unchanged. Anxiolytic-characteristic side-effects (tiredness, drowsiness, etc.) occurred predominantly after the highest doses 0.4 mg suriclone and 1 mg alprazolam.

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“…Single oral doses up to 0.6 mg suriclone were well tolerated in healthy subjects [5]. Dose-dependent toxic effects were dizziness and ataxia.…”

Section: Introductionmentioning

confidence: 97%

Pharmacokinetic and ‐dynamic studies with a new anxiolytic, suriclone, utilizing EEG mapping and psychometry.

Saletu

Grünberger

Linzmayer

et al. 1994

Brit J Clinical Pharma

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“…Studies in healthy subjects resulted in a well tolerated single oral dose up to 0.6 mg suriclone (Shaw et al, 1988). Toxic effects were dose dependent and mainly characterized by balance disorders (dizziness, ataxia).…”

Section: Introductionmentioning

confidence: 99%

Sleep laboratory studies on single dose effects of suriclone.

Saletu

Frey

Grünberger

et al. 1990

Brit J Clinical Pharma

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1 In a double-blind, placebo-controlled sleep laboratory study single doses of suriclone, a new non-benzodiazepine anxiolytic binding to benzodiazepine receptors, were investigated with respect to sleep and awakening. 2 Sixteen healthy young volunteers spent 10 nights in the sleep laboratory: 1 adaptation night, 1 baseline night and 4 drug nights (placebo; 0.2 mg, 0.4 mg suriclone; 2 mg lorazepam as reference drug) and 4 subsequent wash-out nights (drug-interval: 1 week). Somnopolygraphic investigations (22.30 h to 06.00 h) were commenced 0.5 h after drugintake. A self-rating scale for sleep and awakening quality as well as psychometric tests were completed in the morning. 3 Hypnotic effects were most pronounced after lorazepam in regard to total sleep time and sleep efficiency. After lorazepam as well as after 0.4 mg suriclone nocturnal awakenings decreased significantly as compared with placebo, which was reflected in an improved subjective sleep quality after both dosages. Suriclone 0.2 mg did not induce any alterations in all night sleep. 4 In the morning, well-being, drowsiness and reaction time performance deteriorated after lorazepam as compared with placebo but not after suriclone. The latter was significantly superior to lorazepam with respect to subjective awakening quality, wellbeing, emotional rapport, drowsiness and attention. 5 Blood pressure and pulse remained unchanged after all of the drugs. Critical flicker frequency and muscle strength decreased only after lorazepam as compared with placebo.

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“…The sedative activity of suriclone is lower than that of benzodiazepines (Gotfryd, 1984;Gerlach et ul, 1987;McLeod et ul, 1988). Shaw (1988), in comparing neurological effects in normal volunteers, found that a single dose of suriclone 0.2 mg had no greater sedative effect than placebo and that suriclone 0.4 or 0.6 mg was no more sedative than diazepam 1 0 mg. Gilburt er a1 (1992) recently showed that there were no significant effects of suriclone compared to placebo for several psychomotor tests in young and elderly volunteers who received repeated doses (0.2, 0.3, 0.4 mg tid). Allen and Lader (1992) noted an increase in the frequency threshold for CFF when suriclone was administered to normal subjects, suggesting some improvement in sensory perception.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and pharmacodynamic study of suriclone imipramine interaction in man

Perault¹,

Chapelle²,

Bouquet³

et al. 1994

Fundamemntal Clinical Pharma

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Suriclone is a novel cyclopyrrolone exhibiting anxiolytic activity. Twelve healthy Caucasian male volunteers participated in the study. A single dose of suriclone 0.4 mg, imipramine 75 mg, suriclone 0.4 mg + imipramine 75 mg, or placebo was given according to a 4 x 4 Latin-square design in order to assess the effect of drug association on pharmacokinetics and psychomotor performances. Visual analogue scale ratings, critical flicker frequency, choice visual reaction time, and Pauli, picture memory and Sternberg tests were performed before and 1.5, 6 and 9 h after drug administration. Suriclone, with the exception of the Pauli test, had no effect on psychomotor performances. The imipramine-suriclone association appeared to disturb some performances (no statistical significance), probably due to the effect of imipramine. Blood samples were collected for determination of imipramine and suriclone plasma levels respectively by high-performance liquid chromatography and radioimmunoassays. Suriclone AUC, Cmax and Tmax were not affected by imipramine, and reciprocally.

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Comparative Neurologic Effects of Diazepam and Suriclone, a Cyclopyrrolone Anxiolytic

Cited by 7 publications

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Pharmacokinetic and ‐dynamic studies with a new anxiolytic, suriclone, utilizing EEG mapping and psychometry.

Pharmacokinetic and ‐dynamic studies with a new anxiolytic, suriclone, utilizing EEG mapping and psychometry.

Sleep laboratory studies on single dose effects of suriclone.

Pharmacokinetic and pharmacodynamic study of suriclone imipramine interaction in man

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