Gepirone

Antidepressants Desipramine, imipramine, sertraline, fluoxetine, paroxetine, venlafaxine, bupropion, nefazodone, mirtazapine, gepirone, amineptine Mixed findings suggest that better designed studies may find a niche for some of these drugs. Amineptine was effective for withdrawal symptoms. 

Eison, AS, Eison, MS, Stanley, M and Riblet, LA (1986) Serotonergic mechanisms in the behavioural effects of buspirone and gepirone. Pharmac. Biochem. Behav. 24 701-707. 

Monti, J. M., Jantos, H., Silveira, R., Reyes-Parada, M. Scorza, C. (1995a). Sleep and waking in 5,7-DHT-lesioned or (-)-pindolol-pretreated rats after administration of buspirone, ipsapirone, or gepirone. Pharmacol. Biochem. Behav. 52, 305 12. 

Jenkins SW, Robinson DS, Fabre LF Jr, Andary JJ, Messina ME, Reich LA. (1990). Gepirone in the treatment of major depression. J Clin Psychopharmacol. Suppi 10(3) 77S-85S. 

Yocca FD. (1990). Neurochemistry and neurophysiology of buspirone and gepirone interactions at presynaptic and postsynaptic 5-HTlA receptors. J Clin Psychopharmacol. SuppI 10(3) 6S-12S. 

Bianchi G, Caccia S. 1988. Simultaneous determination of buspirone, gepirone, ipsapirone and their common metabolite l-(2-pyrimidinyl)piperazine in rat plasma and brain by high-performance liquid chromatography. J Chromatogr 431(2) 477-480. 

Hippocampus, septum, amygdala, cortical limbic area Agonists buspirone, gepirone, ipsapirone, flesinoxan Antagonists WAY 100135, BMY7378, NAN-190 Possible clinical use of agonists anxiolytics, antidepressants 5-HTi receptors... 

Finally, while on the subject of possible clinical effects of (%2 antagonism, it should be noted that many of the 5-HT, agonists (e.g., buspirone, gepirone, and ipsapirone] that were developed or tested for antianxiety and antidepressant effects are extensively metabolized to l-(2-pyrimidyl]-piperazine, itself an active 0(2-adrenoceptor antagonist (G. Bianchi et al. 1988). Whether this is relevant in vivo in humans remains to be seen. 

S-HTjc, and 5-HTj receptors may be especially involved in the serotonin system s response in anxiety. Most interest has focused around 5-HTj, drugs (buspirone, ipsapirone, gepirone, tandospirone, flesinoxan, and others]. Some preclinical data indicate that antagonists at S-HTj, S-HTj, and 5-HT3 receptors may also exert anxiolytic activity, but so far these findings have not been consistently confirmed in clinical trials. 

Buspirone. Several comparative studies of buspirone and benzodiazepines have reported comparable efficacy in reducing symptoms of anxiety. However, in contrast to benzodiazepines, buspirone is devoid of significant sedative or euphoric effects. Treatment with buspirone and other azaperones, such as gepirone, ipsapirone, and tandospirone, does not result in abuse, addiction, dependence, or withdrawal symptoms [Keppel Hesselink 1992). Buspirone also spares both cognitive and psychomotor performance [N. Sussman 1994). 

Preliminary phase II clinical data have shown that gepirone is an effective anxiolytic that significantly reduces both psychic and somatic symptoms of generalized anxiety disorder. Like buspirone, gepirone does not impair memory, verbal fluency, or psychomotor performance [Harto and Branconnier 1988]. 

Quartermain et al. 1993, 1994 Rowan et al. 1990 Winter and Petti 1987). Also, low doses of gepirone and atropine, which individually fail to modify rat performance in a spatial task, when administered together impair performance [Barrett and Rowan 1990]. Similarly, the selection of a single dose of MDL 73,005EF that did not impair the acquisition or recall of a task in the Morris water maze enhanced the deficits caused by gepirone or atropine [Barrett and Rowan 1992]. 

Bianchi G, Caccia S, Della Vedove F, et al The alpha-2-adrenoceptor antagonist activity of ipsapirone and gepirone is mediated by their common metabolite l-(2-pyrimidinyl -piperazine (PMP). Eur J Pharmacol 151 365-371, 1988... 

Harto N, Branconnier RJ Clinical profile of gepirone, a nonbenzodiazepine anxiolytic. Psychopharmacol Bull 24 154-160, 1988... 

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