Comparative neuropharmacology of buspirone and MJ-13805, a potential anti-anxiety drug

Publisher Website
Google Scholar
Abstract
Buspirone is a clinically efficacious anti-anxiety drug without any other benzodiazepine-like activity. Although buspirone can displace ligands for dopamine (DA) receptors, its equipotent analog, MJ-13805, cannot. Buspirone can potently increase dopaminergic impulse flow and metabolism, primarily due to inhibition of DA autoreceptors. However, MJ-13805 does not block striatal nerve ending DA autoreceptors and slightly increases striatal DA metabolism. Both drugs potently reverse catalepsy due to either DA receptor blockade or DA depletion which indicates an effect within the extrapyramidal system efferent from the DA neuron. Amantadine is at least ten fold less potent than these drugs for reversal of catalepsy. These data indicate that altered dopaminergic neurotransmission may not be important for the anti-anxiety effect of buspirone and that buspirone should be tested for efficacy in various models of movement disorders. The site and mechanism of action for buspirone and MJ-13805 remains obscure. A metabolite of buspirone, 1-piperazinylpyrimidine, does not reverse catalepsy although this drug is known to be active in anti-anxiety screening tests. Thus, buspirone may have separate mechanisms of action for reduction of anxiety and reversal of catalepsy.