Ipsapirone (TVX Q 7821) is a novel legal research chemical and nonbenzodiazepine agent of the azapirones that has strikingly similar chemical structures to benzodiazepines and share a number of pharmacological properties in human studies.
Mechanism of action
Although exact ipsapirone mechanism of action is unknown, this drug is thought to act via effects on central gamma-aminobutyric acid (GABA) neurotransmission. Although efficacy in the treatment of anxiety is clear, the ipsapirone also produce a number of undesirable side effects that frequently limit their usefulness.
For example, sedation, synergism with other central depressants, incoordination, and addictive potential are the most frequently reported adverse side effects of the ipsapirone.
Ipsapirone is equipotent with buspirone in animal models of anxiety and aggression. However, the drugs differ from ipsapirone in that they do not antagonize induced seizures or cause motor incoordination. Clinically, ipsapirone appears to be equipotent with buspirone in the relief of anxiety, yet it has minimal effect on levels of alertness, coordination, or memory. The mechanism of action of both remains unknown. Unlike ipsapirone, buspirone has no effect on the benzodiazepine/GABA receptor complex as studied by radioligand techniques. Ipsapirone does display weak neuroleptic-like activity, although its effects on central dopamine systems is not believed to be related to its anxiolytic effects. Recently, the availability of selective radioligands has allowed 5-HT2 binding sites to be differentiated into 5-HT1A and 5-HTm subtypes.
As a result, the research study analyzed the interactions of buspirone and ipsapirone (TVX Q 7821) with 5-HTiAand 5-HTm sites, as well as with a series of eight other receptor binding sites in brain membranes. The results show that these novel anxiolytics, unlike diazepam and lorazepam, are potent and selective agents at the 5-HT binding site. The major finding of the research study is that TVX Q 7821 are potent and selective inhibitors of 5-HTtA binding sites in brain membranes. These two novel anxiolytics share both structural and pharmacological properties. The drugs display moderate affinity for 5-HT2 sites, but are essentially inactive at 5-HTtB binding sites. In addition, TVX Q 7821 is inactive at benzodiazepine binding sites. A variety of biochemical, pharmacological, and physiological data suggests the existence of multiple serotonin.
Biochemical and physiological data also suggest a potent and selective effect of ipsapirone on central 5-HT receptors. Ipsapirone causes a significant decrease in central 5-hydroxytryptophan formation and also causes a behavioral syndrome consistent with 5-HT receptor activation.
Physiologically, both iontophoretic and systemic administration of ipsapirone cause marked inhibition of dorsal raphe neuronal firing. Unlike DPAT, however, ipsapirone do not possess 5-HT agonist properties in the rat prolactin model.
Behavioral and physiological effects of TVX Q 7821 are almost identical to the effects of buspirone.
In addition, iontophoretic or systemic administration of ipsapirone inhibits raphe cell firing. This physiological effect is identical to the effect of buspirone on raphe cell activity. Behavioral effects of systemic benzodiazepines can also be reproduced by microinjections of the ipsapirone into the dorsal raphe nuclei.