Resistance to the anti-anxiety effect of buspirone in patients with a history of benzodiazepine use. (Letter)

New England Journal of Medicine (Impact Factor: 55.87). 04/1986; 314(11):719-20. DOI: 10.1056/NEJM198603133141121
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    • "Furthermore, a similar tolerance preventing effect has been obtained when morphine (4 mg/kg) was injected on trial 1 and chlordiazepoxide on trial 2 (Leszczuk and Flaherty, 2000). Thus, drugs from three different classes administered on trial 1 offset tolerance to chlordiazepoxide on trial 2. Although these drug interactions have not been reported in the clinical literature, there is evidence that patients with generalized anxiety disorder treated first with benzodiacepines, then with buspirone have reported lack of satisfaction with the effect of buspirone (Schweizer et al., 1986). Therefore, the enhanced effects of chlordiazepoxide following chlordiazepoxide or buspirone treatment obtained in our lab could have interesting involvements for clinical practice and warrant further investigation. "
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    ABSTRACT: It has been repeatedly reported that the anxiolytic action of benzodiazepines in the elevated plus-maze test is abolished in rats that have received a single prior experience of the test apparatus (one-trial tolerance effect). To analyze whether the one-trial tolerance effect of chlordiazepoxide can be influenced by administration of chlordiazepoxide or buspirone on trial 1, male Wistar rats received an IP injection of vehicle, chlordiazepoxide (8 mg/kg) or buspirone (2.5 mg/kg) 30 min. before testing for 5 min. in the plus-maze (trial 1). Seventy-two hours later, the rats received vehicle or chlordiazepoxide 30 min. before the re-exposure to the plus-maze for 5 min. (trial 2). Groups injected with chlordiazepoxide or buspirone on trial 1 and with chlordiazepoxide on trial 2 showed an anxiolytic effect of chlordiazepoxide on trial 2, as opposed to rats injected with vehicle on trial 1 and with chlordiazepoxide on trial 2. As opposed to previous studies, the present results suggest that the influence of prior experience with the plus-maze on the anxiolytic action of chlordiazepoxide during re-exposure seems to depend critically on the drug state in which trial 1 is experienced. These results are discussed with respect to the hypothesis proposed to explain the phenomenon of one-trial tolerance.
    Life Sciences 08/2003; 73(8):1063-74. DOI:10.1016/S0024-3205(03)00416-8 · 2.70 Impact Factor
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    • "deficits New, 1990; Keppel Hesselink, 1992 . However, attempts to substitute buspirone for a benzodiazepine have generally been disappointing because several authors Ž Schweizer et al., 1986; Napoliello and Domantay, 1988; . Ž Ashton et al., 1990 , but not all Pecknold et al., 1985; . "
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    ABSTRACT: Biochemical and electrophysiological approaches were used to assess possible changes in 5-HT1A receptors in the rat brain after long-term treatment with an anxiolytic benzodiazepine. Rats were treated with diazepam (2 mg/kg i.p. daily) during 14 days and then untreated for 1 day (protocol A) or 5 days (protocol C) until they were killed for in vitro investigations on 5-HT1A receptors. In addition, other rats (protocol B) received the same 14-day treatment with diazepam, followed by 1 mg/kg of the drug on days 15 and 16, and 0.5 mg/kg on days 17 and 18, and were killed 24 h after the last injection. In vitro binding and quantitative autoradiographic experiments with [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) showed that the characteristics of 5-HT1A receptor binding sites in the hippocampus and the dorsal raphe nucleus were not significantly altered by the administration of diazepam under the treatment protocols A, B and C. Furthermore, in vitro electrophysiological recordings of serotoninergic neurons in the dorsal raphe nucleus of brain stem slices revealed no modification in the sensitivity of somatodendritic 5-HT1A autoreceptors in rats treated with diazepam according to the protocols A and B. However, under the conditions of protocol C, the potency of 8-OH-DPAT to depress the firing rate of serotoninergic neurons was significantly enhanced, as expected of a hypersensitivity of somatodendritic 5-HT1A autoreceptors. These data support the hypothesis that some functional changes in these receptors could occur during benzodiazepine withdrawal. However, they do not support the idea of a reduced anxiolytic efficacy of 5-HT1A receptor agonists as a result of prior treatment with a benzodiazepine.
    European Journal of Pharmacology 05/1997; 323(2-3):137-48. DOI:10.1016/S0014-2999(97)00032-0 · 2.53 Impact Factor
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    ABSTRACT: High- and commercial-purity specimens of Type 304 SS from BWR absorber rod tubes, irradiated during service to fluence levels of 6 à 10²° to 2 à 10²¹ n{center dot}cm⁻² (E > 1 MeV) in two reactors, were examined by Auger electron spectroscopy to characterize irradiation-induced grain boundary segregation and depletion of alloying and impurity elements, which have been associated with irradiation-assisted stress corrosion cracking (IASCC) of the steel. Ductile and intergranular fracture surfaces were produced by bending of hydrogen-charged specimens in the ultra-high vacuum of Auger microscope. The intergranular fracture surfaces in high-fluence commercial-purity material were characterized by relatively high levels of Si, P, and In segregation. An Auger energy peak at 59 eV indicated either segregation of an unidentified element or formation of an unidentified compound on the grain boundary. In contrast to the commercial-purity material, segregation of the impurity elements and intergranular failure in the high-purity material were negligible for a similar fluence level. However, grain boundary depletion of Cr was more significant in high-purity material than in commercial-purity material, which indicates that irradiation-induced segregation of impurity elements and depletion of alloying elements are interdependent. 7 refs., 10 figs., 2 tabs.
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