Summary
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.
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References
Bannon, M. J., Michaud, R. L., Roth, R. H.: Mesocortical dopamine neurons: Lack of autoreceptors modulating dopamine synthesis. Molec. Pharmacol.19, 270–275 (1981).
Eison, M. S., Taylor, D. P., Riblet, L. A., New, J. S., Temple, D. L., Yevich, J. P.: MJ-13805-1: A potential nonbenzodiazepine anxiolytic. Neurosci. Abst.8, 470 (1982).
Gammans, R. E., Mayol, R. F., Eison, M. S.: Concentration of buspirone and 1-pyrimidinylpiperazine, a metabolite, in rat brain. Fed. Proc.42, 377 (1983).
Glaser, T., Traber, J.: Buspirone: Action on serotonin receptors in calf hippocampus. Eur. J. Pharmacol.88, 137–138 (1983).
Goldberg, H. L., Finnerty, R. J.: The comparative efficacy of buspirone or diazepam in the treatment of anxiety. Am. J. Psychiat.19, 270–275 (1979).
Hjorth, S., Carlsson, A.: Buspirone: Effects on central monoaminergic transmission-possible relevance to animal experimental and clinical findings. Eur. J. Pharmacol.83, 299–303 (1982).
Jacobs, B.: An animal behavior model for studying central serotonergic synapses. Life Sci.19, 777–785 (1976).
Kolasa, K., Fusi, R., Garattini, S., Consolo, S., Ladinsky, H.: Neurochemical effects of buspirone, a novel psychotropic drug, on the central cholinergic system. J. Pharm. Pharmac.34, 314–317 (1982).
Maj, J., Sowinska, H., Baran, L.: The effect of amantadine on motor activity and catalepsy in rats. Psychopharmacol.24, 296–307 (1972).
McMillen, B. A.: Striatal synaptosomal tyrosine hydroxylase activity: A model system for study of presynaptic dopamine receptors. Biochem. Pharmacol.31, 2643–2647 (1982).
McMillen, B. A., Matthews, R. T., Sanghera, M. K., Shepard, P. D., German, D. C.: Dopamine receptor antagonism by the novel anti-anxiety drug, buspirone. J. Neurosci.3, 733–738 (1983).
McMillen, B. A., McDonald, C. C.: Selective effects of buspirone and molindone on dopamine metabolism and function in the striatum and frontal cortex of the rat. Neuropharmacol.22, 273–278 (1983).
Nagatsu, T., Levitt, M., Udenfriend, S.: A rapid and simple radioassay for tyrosine hydroxylase activity. Analyt. Biochem.9, 122–126 (1964).
Riblet, L. A., Taylor, D. P., Eison, M. S., Stanton, H. C.: Pharmacology and neurochemistry of buspirone. J. Clin. Psychiat.43 (Section 2), 11–16 (1982).
Sanghera, M. K., McMillen, B. A., German, D. C.: Buspirone, a nonbenzodiazepine anxiolytic, increases locus coeruleus noradrenergic neuronal activity. Eur. J. Pharmacol.86, 107–119 (1982).
Sanghera, M. K., German, D. C.: Anxiolytics and catecholamine unit activity. J. Neural Transm.57, 267–279 (1983).
Shore, P. A.: On the role of storage granules in the functional utilization of newly synthesized dopamine. J. Neural Transm.39, 131–138 (1976).
Shore, P. A., Dorris, R. L.: On a prime role for newly synthesized dopamine in striatal function. Eur. J. Pharmacol.30, 315–318 (1975).
Tollman, J. F., Paul, S. M., Skolnick, P., Gallagher, D. W.: Receptors for the age of anxiety: Pharmacology of the benzodiazepines. Science207, 274–281 (1980).
Walters, J. R., Roth, R. H.: Dopaminergic neurons: Anin vivo system for measuring drug interactions with presynaptic receptors. Naunyn-Schmiedeberg's Arch. Pharmacol.296, 5–14 (1976).
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McMillen, B.A., Mattiace, L.A. Comparative neuropharmacology of buspirone and MJ-13805, a potential anti-anxiety drug. J. Neural Transmission 57, 255–265 (1983). https://doi.org/10.1007/BF01248997
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DOI: https://doi.org/10.1007/BF01248997