Impairment of learning or memory in the mature and old rat by diazepam

Komiskey, H.L.; Cook, Tim; Lin, Chu-Fang; Hayton, William L.

doi:10.1007/bf00422422

Cited by 25 publications

(7 citation statements)

References 7 publications

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“…1984;Jensen et al 1979;Komiskey et al 1981 ;Oishi et al 1972;Pate1 et al 1979;Scobie and Garske 1970;Soubrie et al 1976). In a recent study it was found that the benzodiazepines diazepam and chlordiazepoxide blocked the acquisition of conditioned fear in mice (Sanger and Joly 1985).…”

mentioning

confidence: 99%

Effects of zolpidem, a new imidazopyridine hypnotic, on the acquisition of conditioned fear in mice

1986

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Benzodiazepines and other compounds which act at benzodiazepine binding sites have been shown previously to attenuate the acquisition of conditioned fear in rodents when administered before the acquisition session, an effect which may parallel the disruption of human memory produced by anxiolytics and sedatives. Such an action is usually, but not invariably, produced by doses which have direct behavioural depressant effects. The present study was carried out to extend previous work by investigating the effects of the hypnotic benzodiazepine triazolam and the nonbenzodiazepines zolpidem and CL 218,872 on the acquisition of learned fear in mice. All these drugs reduced locomotor activity shortly after injection. They also produced disruptions of the acquisition of learned fear. Triazolam exerted behavioural effects similar to those found previously with other benzodiazepines, the does which disrupted the acquisition of conditioned fear being similar to, or lower than, the doses which depressed locomotion. In contrast, the results indicated that zolpidem was more potent at reducing locomotion than at interfering with fear conditioning, a result which may reflect the preferential sedative action of zolpidem.

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confidence: 99%

Effects of zolpidem, a new imidazopyridine hypnotic, on the acquisition of conditioned fear in mice

1986

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“…3). Aged rats also show an enhanced response to diazepam (7,12) and have been used as an animal model. Cerebral diazepam concentrations appear to be similar to those in young animals (7,13) but studies of cerebral receptor binding have given conflicting results.…”

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confidence: 99%

Benzodiazepine hypnotics in the elderly

Cook

1986

Acta Psychiatr Scand

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A review is presented of the changes that occur in the pharmacodynamics of benzodiazepines during normal ageing and as a result of disease. Controlled studies in which subjects of different ages have received single doses of diazepam, temazepam, nitrazepam and flunitrazepam have consistently shown an increase in the response to benzodiazepines in the elderly which is not explained by the effects of disease or by altered plasma concentrations. In general, healthy elderly subjects have a 2-3 fold greater response compared with the young. This change appears to be due to a change in the post-receptor mechanism of action. Cerebral diazepam concentrations are similar in young and elderly rats, though older animals also show an increased response and no consistent changes have been demonstrated in brain receptor binding. However, benzodiazepine-induced increases in GABA binding and GABA-induced increases in post-synaptic inhibition have been reported to be greater in aged animals.Regular daily dosing with most benzodiazepines leads to drug accumulation which is proportional to the elimination half-life. Regular dosing with diazepam, chlordiazepoxide, nitrazepam and flurazepam has also been found to produce more sedation in the elderly, particularly long stay patients who have a high incidence of dementia, and those with a low albumen or chronic renal failure. A controlled trial of 1 week's dosing with 5 mg of nitrazepam or 20 mg of temazepam in elderly in-patients showed that these doses produced significant impairment of psychomotor performance the morning after the last dose. Only about 50% of the patients were affected and many of these were frail patients with mild dementia on rehabilitation or long stay wards. The doses prescribed for these types of patients should not exceed 2.5 mg of nitrazepam or 10 mg temazepam. elderly: A report from the Boston Collaborative Drug Surveillance Program. Br J Clin Pharmacol 1978:5:407-13. 43. Greenblatt D J, Allen M D. Shader R I. Toxicity of hieh dose peterJ Cook, B.Sc, M.D., M.R.C.P.Physician with

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“…(3) In the 3-substituted [l]benzothieno[2,3-c]pyridine series, several esters lOa-c and carboxylic acid 11 were virtually inactive (Table IV). (4) In the same series, aminoethyl carboxamide 12a was very active. However, aminopropyl carboxamide 12b and (dimethylamino)ethyl carboxamide 12c were not active (Table IV).…”

Section: Resultsmentioning

confidence: 94%

“…We describe the synthesis of novel [l]benzothieno[2,3-c]pyridines * Abbreviations: 5-HT, serotonin; BZP, benzodiazepine; CNS, central nervous system; DPPA, diphenyl phosphorazidate; DBU, l,8-diazabicyclo[5. 4.0]undec-7-ene. 1 Synthetic Section.…”

Section: Introductionmentioning

confidence: 99%

Potent anticonflict activity and lessening of memory impairment with a series of novel [1]benzothieno[2,3-c]pyridines and 1,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridines

Kawakubo

Okazaki²,

Nagatani³

et al. 1990

J. Med. Chem.

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[1]Benzothieno[2,3-c]pyridines (10a-c, 11, 12a-t, and 13a,b) and 1,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridines (3a-c, 7, 8a-c, and 9) were synthesized. The compounds are bioisosteres of beta-carbolines and 1,2,3,4-tetrahydro-beta-carbolines where the indole nitrogen is replaced by sulfur. Their pharmacological activity was evaluated in a water lick conflict test in rats and a passive avoidance test in mice. In the 1,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridine series, the presence of ethyl ester (3b) or cyclohexyl carboxamide (7) groups at C-3 conferred good anticonflict activity and lessening of memory impairment, while N-acylation of 3b abolished activity. In the [1]benzothieno(2,3-c]pyridine series, the aminoethyl carboxamide (12a) group at C-3 also conferred activity, but other amides studied were not active. The most potent compounds (3b, 7, and 12a) were also administered orally and had potent anticonflict and antiscopolamine amnesia-reversal activity. These compounds did not bind to the BZP receptor in spite of having structures similar to those of beta-carbolines. Compound 7 bound strongly to 5-HT1A receptors and would be expected to be a novel anxiolytic.

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Impairment of learning or memory in the mature and old rat by diazepam

Cited by 25 publications

References 7 publications

Effects of zolpidem, a new imidazopyridine hypnotic, on the acquisition of conditioned fear in mice

Effects of zolpidem, a new imidazopyridine hypnotic, on the acquisition of conditioned fear in mice

Benzodiazepine hypnotics in the elderly

Potent anticonflict activity and lessening of memory impairment with a series of novel [1]benzothieno[2,3-c]pyridines and 1,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridines

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