Anxiolytics serotonergic

Other serotonergic drugs that are direct receptor agonists or antagonists have been found to have anxiolytic effects (Stahl 1998 Bonhomme and Esposito 1998). A novel class of anxiolytic drugs called azapirones act as partial agonists at 5-HTlA receptors (Yocca 1990). Clinically, they are represented by BuSpar, which was approved for use in 1986 (Eison... 

Farina A, Doldo A, Quaglia MG. 1992. Analysis of new serotonergic anxiolytics by liquid chromatography. J Pharm Biomed Anal 10(10-12) 889-893. 

This mechanism is also consistent with models of fear and anxiety that are primarily based upon pharmacologically derived data. The cumulative reduction in serotonergic impiflse flow to septohippocampal and other Hmbic and cortical areas involved in the control of anxiety is believed to explain the anxiolytic effects of Hgands with selective affinity for the 5-HTia receptor in... 

The biology of the monoamines is described in detail elsewhere. In simple terms, they facilitate transmission in neural pathways that originate in nuclei of the brainstem and have descending projections to the autonomic nervous system and widespread ascending projections to sites in the limbic system and cortex. These pathways modulate many aspects of behavioural function as well as anxiety responses. Of the three monoamines, the role of serotonin in anxiety is best understood, but the picture is complex as increased serotonergic activity may be anxiogenic or anxiolytic depending on the site of action (Bell and Nutt 1998). 

Eison MS The new generation of serotonergic anxiolytics possible clinical roles. Psychopathology 22 [suppl l) 13-20, 1989... 

Jolas T, Schreiber R, Laporte AM, et al Are postsynaptic 5-HTl A receptors involved in the anxiolytic effects of 5-HTlA receptor agonists and in their inhibitory effects on the firing of serotonergic neurons in the rat J Pharmacol Exp Ther 272 920-929, 1995... 

Robinson RG, Boston JD, Starkstein SE, et al Comparison of mania and depression after brain injury causal factors. Am J Psychiatry 145 172-178, 1988 Robinson SE Effect of specific serotonergic lesions on cholinergic neurons in the hippocampus, cortex and striatum, life Sci 32 345-353, 1983 Rodriguez-Sierra JF, Hagley MT, Hendricks SE Anxiolytic effects of progesterone are sexually dimorphic, life Sci 38 1841-1845, 1986 Roemer RA, Dubin WR, Jaffe R, et al An efficacy study of single- versus double-seizure induction with ECT in major depression. J Chn Psychiatry 51 473-478, 1990... 

The startle response test pairs a conditioned stimulus (sound, light) with a footshock to induce an anxiogenic startle response in mice. While the sensitivity of this test to many drugs is yet to be established, benzodiazepine and serotonergic anxiolytics have been effective in reducing the startle response (1). Since this model seems to be unaffected by motor phenotypes, activity levels, or neurological deficits, this test (unlike many other anxiety models discussed here) allows researchers to study mouse anxiety without these confounding factors (see Note 17). 

The link between the serotonergic pathways and the control of anxiety has been further strengthened by the introduction of non-benzodiazepine anxiolytics such as buspirone, ipsapirone and gepirone, which decrease central serotonergic function by stimulating a subclass of 5-HT receptors (5-... 

HT1A), leading to a decrease in serotonergic release. Despite the connection between the decreased functional activity of the serotonergic system and the anxiolytic effects of the benzodiazepines, it would appear that their effect on serotonergic transmission is indirect and probably mediated via a facilitation of the principal inhibitory neurotransmitter, GABA. 

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