Clin Ther. 1988;10(6):740-6.
The safety and usefulness of buspirone as an anxiolytic drug in elderly versus young patients.

Robinson D, Napoliello MJ, Schenk J.

Pharmaceutical Research Development Division, Bristol-Myers Company, Wallingford, Connecticut.

Buspirone, the prototype of the new azaspirodecanedione series of antianxiety drugs, was studied in over 6,000 patients in an open, multicenter trial to confirm its safety and usefulness for anxiety in a typical medical practice setting. Non-psychotic patients with clinically manifest anxiety that required anxiolytic drug therapy were enrolled to receive four weeks of treatment with a fixed dose of buspirone (15 mg/day). Patient data were analyzed according to age: the elderly group comprised 605 patients aged 65 years or older, and the younger group included 5,969 patients less than 65 years old. Both the elderly and younger patients achieved similar relief of anxiety within four weeks based on the Hamilton Anxiety Scale and global assessments of improvement. Most patients (80%) in both groups reported no side effects. Further, the side effect profile in the elderly differed little from that in the younger patients. Overall, the data indicate that buspirone may be administered to patients aged 65 years or older without any special adjustment in dose, does not cause unusual adverse age-related phenomena, and relieves moderate-to-severe symptoms of anxiety in elderly patients.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3219687&dopt=Abstract buspirone Buspar




Pharmacol Biochem Behav. 1988 Oct;31(2):317-9.
The effects of buspirone, a selective anxiolytic, on stress ulcer formation in rats.

Sullivan RM, Henke PG, Ray A.

St. Francis Xavier University, Antigonish, N.S., Canada.

The effects of buspirone hydrochloride were investigated on the formation of cold-immobilization gastric stress ulcers. Low doses significantly attenuated, while higher doses greatly potentiated gastric stress pathology. The dopamine antagonist haloperidol, and the agonist apomorphine respectively, reversed the buspirone effects. The role of dopamine in the expression of buspirone's effects is discussed, although other transmitter systems may mediate some of the actions of buspirone.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3244709&dopt=Abstract buspirone Buspar




J Neurosci. 1988 Jan;8(1):1-11.
Buspirone attenuates synaptic activation of hippocampal pyramidal cells.

Mauk MD, Peroutka SJ, Kocsis JD.

Department of Neurology, Stanford University School of Medicine, California 94305.

The actions of 5-hydroxytryptamine (5-HT) and buspirone, an anxiolytic agent that displays high and selective affinity for 5-HT1A receptor sites, on synaptic activation of hippocampal CA1 pyramidal cells were studied in vitro. Whereas 5-HT application leads to a rapid hyperpolarization and decreased input resistance in pyramidal cells, buspirone has no measurable effects on membrane potential and input resistance. However, unlike 5-HT, buspirone application leads to a gradual and reversible reduction in excitatory postsynaptic potentials (EPSPs) elicited by stimulation of afferents in the stratum radiatum. Concurrent with this attenuation of the EPSP, buspirone decreases the excitability of afferent fibers in the stratum radiatum as evidenced by conduction slowing, increased refractory period, and decreased ability to generate repetitive impulses. 5-HT has no measurable effect on the afferent fibers. The attenuation of the EPSPs and the decrease in afferent fiber excitability appear to be independent of 5-HT receptors as 5-HT neither shares nor antagonizes the effects of buspirone. Thus, both 5-HT and buspirone can contribute to reduced spike activity in pyramidal cells, but they do so via different mechanisms: 5-HT hyperpolarizes pyramidal cells whereas buspirone attenuates their synaptic activation, possibly via action on the presynaptic fibers in the stratum radiatum.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3339401&dopt=Abstract buspirone Buspar




Clin Pharmacokinet. 1988 Mar;14(3):171-7.
Clinical pharmacokinetics of oral buspirone in patients with impaired renal function.

Caccia S, Vigano GL, Mingardi G, Garattini S, Gammans RE, Placchi M, Mayol RF, Pfeffer M.

Istituto di Ricerche Farmacologiche Mario Negri Via Eritrea, Milano.

12 patients with mild to moderate impairment of renal function and 12 healthy subjects each received 20mg buspirone as a single dose in this acute study. Six anuric patients with chronic renal failure were given two 20mg doses of buspirone, the first 2 days before haemodialysis (between dialyses) and the second during hemodialysis (2 hours before dialysis began). The differences between the median pharmacokinetic values of buspirone for healthy subjects, patients with mild to moderate renal impairment, and anuric patients were not statistically significant. Similarly, there were no significant differences between values in mild to moderate renal failure vs healthy subjects. Some of the median pharmacokinetic values for the active buspirone metabolite 1-(2-pyrimidinyl)-piperazine (1-PP), however, differed significantly for anuric patients, compared with healthy subjects or patients with mild to moderate renal impairment. When assessed between and during haemodialysis, the anuric patients had significantly (p less than 0.05) greater pharmacokinetic median values: half-life (t 1/2) = 15.2 vs 9.8 hours; area under the concentration-time curve (AUC) = 604 vs 404 nmol/L.h; and mean residence time (MRT) = 9.28 vs 6.96 hours. No firm recommendation for specific dosage can be made based on the present data. However, it does appear that in patients with mild to moderate renal impairment, the pharmacokinetics of buspirone and its active metabolite 1-PP are similar to those in individuals with normal renal function. For anuric patients higher concentrations of the 1-PP metabolite are attained while they are not undergoing haemodialysis. A dosage reduction of 25 to 50% might be necessary when buspirone is given to anuric pa




Alcohol. 1988 Mar-Apr;5(2):147-52.
Buspirone alters alcohol drinking induced in rats by tetrahydropapaveroline injected into brain monoaminergic pathways.

Privette TH, Hornsby RL, Myers RD.

Department of Pharmacology, East Carolina University School of Medicine, Greenville, NC 27858.

The effect of the novel anxiolytic, buspirone, administered systemically was determined in Sprague-Dawley rats induced to drink ethyl alcohol chronically by repeated microinjections of 25 ng/microliter tetrahydropapaveroline HBr (THP) into brain-stem monoaminergic pathways. Self-selection of alcohol in concentrations from 3% to 30% was determined for each rat in a free-choice drinking situation with water available as the alternative fluid. After stereotaxic implantation of guide tubes, THP was microinjected repeatedly into striatal lemniscal and preoptic sites which were found to mediate significant increases in alcohol preference. After the baseline level of intake of a single, maximally preferred alcohol concentration was established, each rat was treated with either saline vehicle or buspirone given intramuscularly b.i.d. in doses of 5.0 mg/kg or 20 mg/kg. Overall, the repeated administration of either dose of buspirone produced a significant decrease in the voluntary alcohol intake of the rats as measured by the proportion measure and absolute g of alcohol ingested. However, the alteration in drinking varied from animal to animal with respect to both magnitude and duration of the anxiolytic's effect. The response to buspirone seemed to be dependent in part on the individual site in each animal at which THP had been infused to evoke alcohol intake. Post-mortem histological analysis revealed that buspirone-treated rats reduced alcohol consumption by 83% if THP had been microinjected into substantia nigra; by 60% if given in the nucleus accumbens-preoptic area; and by 34% when injected into the medial lemniscus-zona incerta. These results suggest, therefore, that buspirone can exert a specific effect in




Pharmacol Biochem Behav. 1988 Apr;29(4):823-6.
Multiple and complex effects of buspirone on central dopaminergic system.

Algeri S, De Luigi A, De Simoni MG, Imeri L, Marconi M, Nava S, Perego C, Sacchetti G.

Istituto di Ricerche Farmacologiche, Mario Negri, Milano, Italia.

The effects of the anxiolytic drug buspirone and its metabolite 1-PP on the dopaminergic system were investigated. A single buspirone administration was found to decrease DA levels and increase its metabolite DOPAC in striatal samples. The levels of the other DA metabolite, 3MT, were unaffected; however its formation rate after inhibition of its metabolism, was found to be increased by buspirone. 1-PP did not affect either DOPAC or 3MT levels and formation. Striatal microdialysis showed that buspirone enhances DA release. In vivo voltammetry indicates that the increase of DA metabolism is identical in the two sampled dopaminergic areas, striatum and nucleus accumbens. On the basis of the results obtained ex vivo and in vivo the multiple effect of buspirone on dopaminergic system is discussed.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3413206&dopt=Abstract buspirone Buspar




Psychopharmacol Bull. 1990;26(3):393-405.
Buspirone challenge: preliminary evidence for a role for central 5-HT1a receptor function in impulsive aggressive behavior in humans.

Coccaro EF, Gabriel S, Siever LJ.

Department of Psychiatry, Medical College of Pennsylvania, Eastern Pennsylvania Psychiatric Institute, Philadelphia 19129.

The prolactin (PRL) response to challenge with buspirone hydrochloride, a serotonin1a (5-HT1a) receptor agonist, was examined in 5 healthy male volunteers and in 10 healthy male and female patients with primary DSM-III personality disorder. In healthy volunteers, pretreatment with the nonselective 5-HT receptor antagonist, metergoline (4 mg p.o.) completely suppressed the maximal PRL response to buspirone challenge. Pretreatment with the nonselective beta-adrenergic/5-HT1-like antagonist, pindolol suppressed the maximal PRL response to buspirone challenge depending upon dose (i.e., between 49 to 90% suppression at best dose). In personality disorder patients, PRL responses to buspirone challenge correlated inversely with self-assessed "irritability" (r = -.76, n = 10, p less than .01). These data suggest that the PRL response to buspirone challenge reflects the responsivity of 5-HT1a receptors in the limbic-hypothalamus in humans and that reduced sensitivity of these receptors is associated with an important component of impulsive aggressive behaviors in personality disorder patients.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2274641&dopt=Abstract buspirone Buspar




Life Sci. 1987 May 18;40(20):2017-24.
Presynaptic control of dopamine metabolism in the nucleus accumbens. Lack of effect of buspirone as demonstrated using in vivo voltammetry.

Louilot A, Le Moal M, Simon H.

Buspirone is a non-benzodiazepine drug with anxiolytic properties. It has been reported to induce a marked increase in the metabolism of dopamine in the striatum and the nucleus accumbens which is similar to that induced by neuroleptics. It has been suggested that the effect observed in the striatum reflects an action of buspirone on dopaminergic autoreceptors in both terminals and cell bodies. In the present study, presynaptic effects of buspirone on dopaminergic metabolism in the nucleus accumbens were investigated, and they were compared to the effects of the classical neuroleptic, haloperidol. Dopaminergic terminals were isolated by infusion of tetrodotoxin into the median forebrain bundle in order to evaluate the effects of buspirone and haloperidol on presynaptic receptors. Changes in dopamine metabolism were determined by in vivo voltammetry. Buspirone administered after interruption of the impulse flow did not affect dopamine metabolism. In contrast haloperidol treatment led to an increase in metabolism of dopamine. It is concluded that buspirone did not act at the presynaptic level and furthermore on dopaminergic autoreceptors.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3573992&dopt=Abstract buspirone Buspar