New concepts on the mechanism of action of benzodiazepines

Costa, E.; Guidotti, Alessandro; Mao, Chengwen; Suria, Amin

doi:10.1016/0024-3205(75)90501-9

Cited by 547 publications

(95 citation statements)

References 35 publications

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“…The anticholinesterase physostigmine acts in an antagonistic fashion to the effects of hyoscine upon memory, but has no such antagonistic effect on a diazepam-induced memory deficit (Ghoneim & Mewaldt, 1977). On the other hand it has been suggested that the action of diazepam may be GABA-ergic (Costa, Guidotti, Mao & Suria, 1975).…”

Section: Introductionmentioning

confidence: 99%

Drugs and human memory: effects of low doses of nitrazepam and hyoscine on retention.

Jones¹,

Jones²,

Lewis³

et al. 1979

Brit J Clinical Pharma

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1 The effects of diazepam (5 mg) and hyoscine hydrobromide (0.3 mg) were assessed in two memory tasks: short-term retention of digit strings and the free recall of items from categorizable lists. 2 One hundred and two healthy subjects were tested in an independent-groups design. Subjects were assigned randomly to either placebo, diazepam or hyoscine groups. Treatments were administered orally under double-blind conditions. 3 The short-term, retention of digits was impaired to an equivalent degree and locus for both drugs (P < 0.05). This effect was ascribed to the action on primary memory. 4 The drugs produced no significant effects on the recall of categorizable lists either in terms of the number of words recalled or the cohesiveness of categorical recall. S These results demonstrate that drugs of different pharmacological actions produce isomorphic psychological deficits in memory and that 'anti-memory' effects on one task should not be extrapolated to all aspects of memory.

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Section: Introductionmentioning

confidence: 99%

Drugs and human memory: effects of low doses of nitrazepam and hyoscine on retention.

Jones¹,

Jones²,

Lewis³

et al. 1979

Brit J Clinical Pharma

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“…There are numerous reports supporting the idea that benzodiazepines have a facilitatory activity on GABAergic processes (16)(17)(18)(19)(29)(30)(31)(32). On the other hand, Martin and Candy (33) and Briley and Langer (34) reported that the GABA receptor agonists increased, while the GABA receptor antagonist decreased the affinity of benzodiazepines for their specific binding sites.…”

Section: Discussionmentioning

confidence: 98%

“…There is a growing body of evidence indicating the possible involvement of y-aminobutyric acid (GABA) system in the effects of benzodiazepines such as muscle relaxation and convulsion antagonism (19)(20)(21)(22). If GABAergic related mechanisms are also involved in the effects of anxiolytics on these conditioned behaviors, the effects may be influenced by drugs acting on the GABA system.…”

mentioning

confidence: 99%

Avoidance enhancement and discriminative response control by anxiolytics with drugs acting on the GABA system.

Oka¹,

Yamada²,

Yoshida³

et al. 1980

Jpn.J.Pharmacol

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Abstract-Two types of conditioned behaviors were investigated for the purpose of evaluating anxiolytic drugs. A conditioning procedure used was an active avoidance in poorly-performing mice. Chlordiazepoxide, diazepam, chlorazepate and meprobamate increased the avoidance rate, while chlorpromazine, haloperidol and nortriptyline did not produce such an effect. The effect of diazepam was potentiated by r-aminobutyric acid (GABA) and aminoxyacetic acid (AOAA) and antagonized by picrotoxin and thiosemicarbazide, but was influenced little by spiroperidol, a-methyltyrosine, phenoxy benzamine and levallorphan.In addition, the effect of other anxiolytics was potentiated by AOAA and antagonized by picrotoxin.Biperiden, methamphetamine, caffeine and morphine also induced an avoidance enhancement, which was not influenced by AOAA. A drug discrimination experiment was also performed using a milk-reinforced two-lever operant method.In the rats trained to discriminate phenobarbital from saline, diazepam produced a dose-related phenobarbital-lever selection, which was potentiated by AOAA and antagonized by picrotoxin.Chlordiazepoxide, chlorazepate and meprobamate also elicited responses on the phenobarbital-lever.On the other hand, haloperidol, nortriptyline, biperiden, methamphetamine, caffeine and morphine produced a saline-lever selection, at the doses tested. These results suggest that, among several drugs tested, the avoidance enhancement and discriminative response control by anxiolytics may be closely linked with the GABA system. Among the numerous methods used to evaluate anxiolytic drugs, the conditioning procedures such as conditioned suppression (1, 2) and Geller's conflict test (3, 4) are available for indexes of conditioned "anxiety" and to demonstrate marked difference between anxiolytics and the other classes of drugs. It is most difficult, however, in these tests to produce appropriate response patterns, because environmental contingencies such as re inforcement schedule, duration and frequency of discriminative stimuli and the extent of punishment determined the degree of response suppression and drug effects. Under some conditions, amphetamine (5, 6), morphine (7,8), chlorpromazine (9, 10) and reserpine (11) also alleviate the response suppression induced by punishment.The effects of anxiolytics on the other conditioned behaviors have also been examined by several investigators. Takaori et al. (12,13) reported that benzodiazepine anxiolytics enhanced the conditioned avoidance response of poorly-performing animals in both Sidman avoidance and shuttle box avoidance procedures. However, this effect was not specific for anxiolytics since several non-anxiolytics were also effective in similar avoidance tests

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“…Actions of pentobarbital and diazepam were indicated to be mediated by the central GABA-ergic system (29)(30)(31)(32).…”

Section: Discussionmentioning

confidence: 99%

Effects of brain biogenic amines on ethanol withdrawal reactions and the development of ethanol dependence in mice.

Yamanaka

1982

Jpn.J.Pharmacol

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Abstract-Micewere made physically dependent on ethanol by a four-day period of ethanol inhalation. A single injection of L-dopa tended to enhance ethanol withdrawal reactions and 5HTP tended to suppress it. Daily treatment with PCPA and L-dopa or pretreatment with 60HDA tended to modify the severity of withdrawal reactions. PCPA slightly decreased the severity, 60HDA tended to aggravate the severity, and L-dopa tended to decrease the severity. The simultaneous estimation of brain biogenic amine levels suggests that 5HT and DA may be involved in the development of physical dependence on ethanol. Treatment with neuropharmacological drugs during ethanol withdrawal modified the severity of ethanol withdrawal reactions. Pentobarbital and diazepam completely suppressed ethanol withdrawal reactions. G H BA and reserpine suppressed the severity and haloperidol, imipramine, and methylphenidate aggravated it. The simul taneous estimation of brain catecholamine levels suggests that suppression of ethanol withdrawal reactions consistently results from the decreased activities of either noradrenergic or dopaminergic neurons. However, the effects of biogenic amines on ethanol withdrawal reactions may be different from those on the development of physical dependence on ethanol.

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New concepts on the mechanism of action of benzodiazepines

Cited by 547 publications

References 35 publications

Drugs and human memory: effects of low doses of nitrazepam and hyoscine on retention.

Drugs and human memory: effects of low doses of nitrazepam and hyoscine on retention.

Avoidance enhancement and discriminative response control by anxiolytics with drugs acting on the GABA system.

Effects of brain biogenic amines on ethanol withdrawal reactions and the development of ethanol dependence in mice.

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