Anxiolytic activity

Newel experimental approaches to anxiety therapy include ligands interacting with the ligand-gated ion channels that are selectively activated by nicotine, C qH 4N2 (87), the well-known active ingredient of cigarettes which has anxiolytic actions (42). Cholecystokinin B receptor ligands, specifically the dipeptoid, CI-988 [130404-91 -0] 02 1142 40 (88) have demonstrated anxiolytic activity ia preclinical models (43). 

Displacement of the activated halogen in 9 led to a series of compounds with marked anxiolytic activity in laboratory animals. It soon became apparent that fate had intervened a second time in the chemistry of this series the compounds were not... 

The anxiolytic agent buspirone (131) is notable for the fact that it does not interact with the receptor for the benzodiazepines. This difference in biochemical pharmacology is reflected in the fact that buspirone (131) seems to be devoid of some of the characteristic benzodiazepine side effects. The spiran function is apparently not required for anxiolytic activity. Alkylation of 3,3-dimethylglutarimide with dichlorobutane in the presence of strong base yields the intermedi-... 

Venlafaxine extended release, duloxetine, paroxetine, and escitalopram are FDA approved for treatment of GAD. Sertraline is also effective. Acute response and remission rates are approximately 65% and 30%, respectively. Imipramine may be used when patients fail to respond to selective serotonin reuptake inhibitors (SSRIs). In one trial, diazepam, trazodone, and imipramine had greater anxiolytic activity than placebo. 

Another SNRI, bicifadine (20), formerly under clinical development for chronic low back pain, is now being developed for neuropathic pain [65,66]. Flufenoxine, also known as F-98214-TA (21), was reported to display greater potency than several reference antidepressants in animal models predictive of antidepressant and anxiolytic activities [67]. SEP-227162 (structure undisclosed) is another SNRI reportedly undergoing clinical development [68]. 

Studies on the anxiolytic diazepams have been extended to compounds in which the imino nitrogen is replaced by a carbon function. A monoaza analogue (3) of diazepam was examined for anxiolytic activity by the antipentylenetetrazole test in rats, but it was found to be inactive [5]. Two 4-methyl deriva-... 

Decker MW, Brioni JD, Sullivan JP, Buckley MJ, Radek RJ, Raszkiewicz JL, Kang CH, Kim DJ, Giardina WJ, Wasicak JT, et al. (1994). (S)-3-methyl-5-(l-methyl-2-pyrrolidinyl)isoxazole (ABT 418) a novel cholinergic ligand with cognition-enhancing and anxiolytic activities II. In vivo characterization. J Pharmacol Exp Ther. 270(1) 319-28. 

Bhattacharya SK, Mitra SK. (1991). Anxiolytic activity of Panax ginseng roots an experimental study. J Ethnopharmacol. 34(1) 87-92. 

Satyan KS, Jaiswal AK, Ghosal S, Bhattacharya SK. (1998). Anxiolytic activity of ginkgolic acid conjugates from Indian Ginkgo biloba. Psychopharmacology (Berlin). 136(2) 148-52. 

The disinhibitory effects of 5-HT3 receptor antagonists are now well documented [29, 30]. These compounds act to restore normal behaviour to animals in conditions which are mildly aversive, such as a novel brightly lit test area. Such effects may be predictive of anxiolytic activity. An example of such disinhibition is the effect of ondansetron in the rat social interaction test in which the level of interaction between two rats is measured under certain defined conditions [29]. In non-aversive conditions this type of behaviour is quite marked, but it is suppressed in novel highly illuminated conditions. Ondansetron overcomes this suppression, as do known anxiolytics such as diazepam. 

Anxiolytic activity Several novel anxiolytics (e.g. buspirone, ipsapirone) are 5-HTia partial agonists 5-HT2 and 5-HT3 antagonists have anxiolytic properties... 

Treit D, Fundytus M (1989) Thigmotaxis as a test of anxiolytic activity in rats. Pharmacol Biochem Behav 31 959-962... 

Various compounds that decrease glutamatergic transmission via blockade of NMDA or group I mGlu receptors produce anxiolytic- and antidepressantlike actions in animal tests and models. Anxiolytic activity resulting from NM DA receptor antagonism was reported as early as 1986 (Bennett and Amrick... 

Kanthan R, Shuaib A (1995) Clinical evaluation of extracellular amino acids in severe head trauma by intracerebral in vivo microdialysis. J Neurol Neurosurg Psychiatry 59 326-327 Karcz-Kubicha M, Jessa M, Nazar M, et al (1997) Anxiolytic activity of glycine-B antagonists and partial agonists—no relation to intrinsic activity in the patch clamp. Neuropharmacology 36 1355-1367... 

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