J Chromatogr. 1991 May 3;566(1):250-6.
Sensitive determination of buspirone in serum by solid-phase extraction and two-dimensional high-performance liquid chromatography.

Kristjansson F.

Delta Ltd., Hafnarfjordur, Iceland.

A selective and sensitive determination of buspirone in serum by high-performance liquid chromatography is described. The procedure is based on separation on a C18 column. A solid-phase extraction procedure is used for sample clean-up. The retention on the first column is based on the hydrophobic interaction of buspirone with the stationary phase, and the retention on the second column is based on ionic interactions due to the presence of sodium lauryl sulphate in the mobile phase as well as hydrophobic interaction. This allows for good separation of buspirone from impurities and consequently allows lower detection limits than previously reported for liquid chromatographic methods. Detection by ultraviolet absorbance gives a detection limit of 0.2 ng/ml.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1885719&dopt=Abstract buspirone Buspar




Pharmacol Biochem Behav. 1991 Jun;39(2):275-8.
Comparison of the effects of buspirone and chlordiazepoxide on successive discrimination.

Panickar KS, McNaughton N.

Department of Psychology, University of Otago, Dunedin, New Zealand.

Buspirone is a novel anxiolytic which does not share the muscle relaxant, anticonvulsant and sedative properties of classical anxiolytics such as the benzodiazepines. It has variable effects in conflict tasks based on shock which normally show consistent effects with classical anxiolytics. The present experiment investigated the effects of buspirone on successive discrimination, a conflict task employing omission of reward rather than shock. Buspirone (3.3, 1.1 and 0.3 mg/kg, IP) and chlordiazepoxide (5 and 20 mg/kg, IP) were administered to separate groups of rats throughout acquisition of a visual successive discrimination. Chlordiazepoxide released nonrewarded responding in a dose-related fashion. The effects of buspirone were qualitatively similar in releasing response suppression but were both less in magnitude and less clearly related to dose. The experiment shows that the action of buspirone in successive discrimination tasks does not depend on the use of shock but, rather, appears to be a genuine failure to fully release behavioural inhibition.

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J Pharmacol Exp Ther. 1990 Aug;254(2):420-6.
Effects of buspirone and related compounds on suppressed operant responding in rats.

Sanger DJ.

Synthelabo Recherche (L.E.R.S), Bagneux, France.

The novel anxiolytic drug buspirone and its analogues, gepirone and ipsapirone, have behavioral effects that differ substantially from those of other anxiolytics such as benzodiazepines and barbiturates. In particular, buspirone does not consistently produce large increases in rates of responding suppressed by punishment in rodents or primates. To study the effects of buspirone and other compounds on suppressed operant responding in rats, two procedures were used. In the first, food-reinforced responding was suppressed during a stimulus associated with response-produced electric shocks (punishment). Chlordiazepoxide produced large increases in rates of punished responding, but neither buspirone nor ipsapirone gave rise to a similar effect. In a second experiment, food-reinforced responding was suppressed during a stimulus that terminated with an unavoidable shock (conditioned emotional response). Chlorodiazepoxide and clorazepate increased suppressed response rates at low doses and decreased nonsuppressed responding at higher doses, giving rise to dose-related increases in suppression ratios. The effects of buspirone, gepirone and ipsapirone were similar to those of the benzodiazepines with ipsapirone producing particularly marked increases in responding during the pre-shock stimulus. 8-Hydroxy-2-(di-n-propylamino)tetralin did not consistently give rise to the same effect. In addition, similar effects were not produced by haloperidol, imipramine, morphine or idazoxan. Haloperidol and morphine decreased nonsuppressed responding without changing rates of suppressed responding or suppression ratios. Imipramine decreased rates of both nonsuppressed and suppressed responding and idazoxan decreased suppression ratios. The conditioned emotional response procedure may be more sensitive for assessing the behavioral ef




Br J Pharmacol. 1990 Sep;101(1):171-7.
Actions of 5-HT1 ligands on excitatory synaptic transmission in the hippocampus of alert rats.

O'Connor JJ, Rowan MJ, Anwyl R.

Department of Pharmacology and Therapeutics, Trinity College, Dublin, Ireland.

1. The effects of 5-hydroxytryptamine1 (5-HT1) ligands on excitatory synaptic transmission were examined in the stratum radiatum of the CA1 region of the dorsal hippocampus of alert, gently restrained, rats. 2. 5-HT produced a dose-dependent reduction in the amplitude of the electrically evoked population excitatory postsynaptic potential (e.p.s.p.) when injected directly into the hippocampus via a cannula (dose producing 50% maximum inhibition, ED50 = 0.46 microgram). 3. Direct intrahippocampal (i.h.) application of buspirone (ED50 = 0.29 microgram), gepirone (1 microgram), ipsapirone (1 microgram), BMY 7378 (0.1 microgram) and 5-carboxamidotryptamine (5-CT, 0.02 microgram) mimicked the inhibitory effect of 5-HT. 4. Systemic injection of buspirone (ED50 = 0.88 mg kg-1, i.p.), BMY 7378 (0.01 mg kg-1, i.p.) and RU 24969 (1 mg kg-1, s.c.) also had an inhibitory effect on the amplitude of the e.p.s.p. 5. Injection of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 2 micrograms) and spiroxatrine (1 microgram) i.h. alone had no effect on the e.p.s.p. amplitude but prevented the inhibitory effect of 5-HT. 6. Systemic injection (i.p.) of methysergide (5 mg kg-1) and spiroxatrine (1 mg kg-1) antagonized the inhibitory effect of buspirone whereas pretreatment with ketanserin (1 mg kg-1), trifluoperazine (1 mg kg-1) and idazoxan (1 mg kg-1) had no effect on the response to buspirone. 7. It is concluded that hippocampal synaptic transmission is highly sensitive to the agonist and antagonist properties of 5-HT1 ligands in the alert rat.

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J Chromatogr. 1992 Mar 13;575(1):117-21.
Simultaneous high-performance liquid chromatographic analysis of buspirone and its metabolite 1-(2-pyrimidinyl)-piperazine in plasma using electrochemical detection.

Betto P, Meneguz A, Ricciarello G, Pichini S.

Istituto Superiore di Sanita, Rome, Italy.

A selective and sensitive high-performance liquid chromatographic method with coulometric detection is described for the quantitation of buspirone and its active metabolite, 1-(2-pyrimidinyl)piperazine, in plasma samples of mice treated orally with buspirone (10 mg/kg body weight). The analytes are extracted with a carboxylic acid solid-phase extraction column before chromatography. A dual-electrode electrochemical detector is used. The limit of detection is 50 pg for buspirone and 35 pg for 1-(2-pyrimidinyl)piperazine.

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J Am Board Fam Pract. 1991 Mar-Apr;4(2):89-94.
Buspirone effect on tobacco withdrawal symptoms: a pilot study.

Robinson MD, Smith WA, Cederstrom EA, Sutherland DE.

Department of Family Practice, Carolinas Medical Center, Charlotte, NC.

Tobacco withdrawal symptoms hamper smoking cessation. This was a pilot study of buspirone, a new azapirone anxiolytic, for tobacco withdrawal. Thirteen smokers entered an open clinical trial. Smokers were titrated to 30 mg/day of oral buspirone for 2 weeks prior to cessation. Tobacco withdrawal and Spielberger state-anxiety scales were used at baseline, on the quit date, and then at 24 hours, 48 hours, 1 week, and 2 weeks after abrupt cessation. At the final visit, smokers compared their withdrawal experience with previous cessation attempts. Two patients (15 percent) could not tolerate the medication and did not attempt smoking cessation. Of the remaining 11 smokers, 3 (27 percent) rated withdrawal relief "very definite," 6 (55 percent) "moderate," and 2 (18 percent) "slight." More than two-thirds of the smokers believed that their difficulty concentrating, craving, restlessness, and anxiety were improved compared with earlier tobacco withdrawal attempts. Five patients (46 percent) reported decreased smoking urges during the 2-week medication titration period. Tobacco withdrawal symptoms and state-anxiety scores changed significantly during the study (P less than 0.05). These results are encouraging, but they should be interpreted with caution because of the small sample size and lack of placebo control. Buspirone effect on tobacco withdrawal symptoms should be studied in a randomized, controlled clinical trial.

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Psychopharmacology (Berl). 1992;108(3):289-94.
Effects of buspirone and gepirone on i.v. cocaine self-administration in rhesus monkeys.

Gold LH, Balster RL.

Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0613.

Buspirone and gepirone were evaluated as potential pharmacotherapies for cocaine abuse by studying the effects of acute and repeated treatment on IV cocaine self-administration in rhesus monkeys. Chlorpromazine was also evaluated as a positive control. Effects of IV drug pretreatments were tested during daily 60-min sessions with lever-pressing reinforced under a fixed-ratio 10 schedule of 0.02 or 0.05 mg/kg cocaine infusions. Acute pretreatment with buspirone (0.1 and 0.3 mg/kg, IV) increased rates of cocaine self-administration without disrupting food pellet consumption. Some doses of buspirone also produced changes in rates of cocaine self-administration without altering the within-session pattern of responding. In contrast, acute doses of gepirone had little effect on rates of cocaine self-administration, while disruptions in food consumption and changes in the within-session pattern of cocaine self-administration were obtained at the highest dose of gepirone tested (1.0 mg/kg). When either buspirone (0.1 and 0.3 mg/kg, IV) or gepirone (0.1 mg/kg, IV) were administered daily for 10 days, consistent effects on cocaine self-administration were not observed. Thus, the effects of acute buspirone administration on cocaine-maintained behavior were similar to the effects produced by chlorpromazine and other dopaminergic antagonists, whereas, gepirone was ineffective. These results provide some support for further evaluation of buspirone as a potential pharmacotherapy for cocaine abuse, although its lack of efficacy with repeated treatment is not encouraging. The negative results with gepirone provide less rationale for continued investigations with this drug, possibly because of its lesser involvement than buspirone with




Pharmacol Biochem Behav. 1991 Mar;38(3):611-6.
Behavioral effects of chronic buspirone administration in the pigeon: comparison to midazolam.

Nader MA.

Department of Psychiatry, Pritzker School of Medicine, University of Chicago, IL 60637.

The effects of acute and chronic administration of buspirone and midazolam were examined in White Carneau pigeons (N = 5) responding under a fixed-ratio 30 (FR 30) schedule of food presentation. Each drug was studied in all pigeons. For three pigeons, buspirone was studied before midazolam, while the order was reversed for the other two subjects. For each drug, a dose-response curve was determined before (prechronic) and two weeks after (postchronic) discontinuation of chronic administration. Prior to chronic drug administration, buspirone (0.3-5.6 mg/kg) and midazolam (0.1-3.0 mg/kg) decreased response rates in all subjects, in a dose-dependent manner. Midazolam was more potent than buspirone; midazolam's ED50 (95% C.I.) was 0.53 (0.41-0.69) mg/kg compared to 2.55 (1.48-4.41) mg/kg for buspirone. For each subject, the lowest dose that decreased responding by at least 50% was administered daily, immediately before the session, for up to 6 weeks. At the lowest daily dose of buspirone, complete recovery of baseline rates was observed in 3 pigeons. However, when the buspirone dose was increased, responding remained below control rates in all but one pigeon. During chronic midazolam administration, tolerance developed to the rate-decreasing effects of midazolam in 4 subjects. When saline was substituted for buspirone or midazolam, suppressed responding returned to predrug rates in all subjects. When the dose-response curves were redetermined, the postchronic ED50 for buspirone was 3.79 (2.10-6.82) mg/kg, which was not significantly different from the prechronic ED50, suggesting that tolerance did not develop to buspirone's rate-decreasing effects.(ABSTRACT TRUNCATED AT 250 WORDS)

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