Description
Buspirone hydrochloride is an anxiolytic agent indicated for the management of
anxiety disorders with or without accompanying depression. In contrast to the
benzodiazepines, buspirone does not interact with alcohol, and lacks sedative,
anticonvulsant, and muscle relaxant effects, and abuse potential.
Chemical Properties
White Solid
Originator
Mead Johnson (USA)
Uses
anxiolitic;serotonin receptor agonist
Uses
Non-benzodiazepine anxiolitic; 5-hydroxytryptamine (5-HT1) receptor agonist.
Uses
Non-benzodiazepine anxiolytic; 5-hydroxytryptamine (5-HT1) receptor agonist.
Definition
ChEBI: A hydrochloride salt resulting from the reaction of equimolar amounts of buspirone and hydrogen chloride.
Manufacturing Process
There is the 3 methods for preparing of 8-azaspiro(4.5)decane-7,9-dione, 8-
(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl) monohydrochloride (U.S. Patent
3,717,634). One of them is follows: a mixture of 0.1 mole of the substituted
glutaric anhydride, 0.1 mole of l-(4-aminobutyl)-4-(2-pyrimidinyl)piperazine
(U.S. Pat. 3,398151), and 300 ml of pyridine was refluxed until imide
formation was completed. The degree of reaction was readily followed by
taking an aliquot portion of the reaction mixture, removing the solvent, and
obtaining the infrared absorption spectrum of the residue. When reaction is
complete, the spectrum exhibited typical infrared imide bands at 1701 and
1710 cm-1 whereas if incomplete, the infrared spectrum contains amide and
carboxyl absorption bands at 1680, 1760 and 3300 cm-1.
1-(3-Cyanopropyl)-4-(2-pyrimidinyl)-piperazine. A mixture of 1-(2-
pyrimidinyl)piperazine (6.0 g, 0.04 mole), 4.6 g (0.044 mole) of 3-
chloropropionitrile and sodium carbonate (4.24 g, 0.04 mole) in 50 ml of nbutanol
was gently refluxed for 16 hours. The reaction mixture was
concentrated in vacuo and the residual oil dissolved in about 100 ml of
cyclohexane. On standing a white crystalline material separated which was
crystallized from cyclohexane to provide 6.5 g (yield 70%) of the cyano intermediate, m.p. 56.6-58°C. A solution of 11.5 g (0.05 mole) of 1-(3-
cyanopropyl)-4-(2-pyrimidinyl)piperazine in 150 ml of absolute ethanol was
saturated with ammonia. W-6 Raney nickel catalyst was added and the
mixture hydrogenated under 1200 p.s.i. When the hydrogenation was
completed the mixture was filtered and the residual oil distilled under reduced
pressure to provide 8.2 g (70% ) of 1-(4-aminobutyl)-4-(2-
pyrimidinyl)piperazine, b.p. 143-146°C at 0.1 mm. (nD
26 = 1.5582).
The azospiroalkenedione 8-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-8-
azaspiro[4.5]decane-7,9-dione was purified as free base by stripping off the
pyridine solvent and crystallizing the residue from a suitable solvent or by
vacuum distillation thereof hydrochloric salt of it was prepared by treating of
an ethanol solution of free base with equimolar amount of HCl.
Brand name
Buspar (Bristol-Myers Squibb);BESPAR.
Therapeutic Function
Anxiolytic
General Description
Pharmaceutical secondary standards for application in quality control provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards
Biological Activity
Classic 5-HT 1A partial agonist with relatively high affinity (K i = 9.3 - 29.5 nM). A clinically effective anxiolytic.
Biochem/physiol Actions
5-HT1A serotonin receptor agonist; anxiolytic.
Veterinary Drugs and Treatments
Buspirone may be effective in treating certain behavior disorders
in dogs and cats, principally those that are fear/phobia related and
especially those associated with social interactions. Buspirone may
also be useful for urine spraying or treatment of motion sickness
in cats.
Drug interactions
Potentially hazardous interactions with other drugs
Antibacterials: concentration increased by
erythromycin - reduce dose; concentration reduced
by rifampicin.
Antidepressants: avoid with tranylcypromine; risk of
severe hypertension with MAOIs - avoid.
Antifungals: concentration increased by itraconazole
- reduce dose.
Antipsychotics: enhanced sedative effects;
haloperidol concentration increased.
Antivirals: concentration increased by ritonavir,
increased risk of toxicity.
Calcium-channel blockers: concentration increased
by diltiazem and verapamil - reduce dose.
Grapefruit juice: concentration increased by
grapefruit juice - reduce dose.
Methylthioninium: possible risk of CNS toxicity -
avoid if possible.
Metabolism
Systemic bioavailability of buspirone is low because of
extensive first-pass metabolism. Metabolism in the liver is
extensive via the cytochrome P450 isoenzyme CYP3A4;
hydroxylation yields several inactive metabolites and
oxidative dealkylation produces 1-(2-pyrimidinyl)-
piperazine, which is reported to be about 25% as potent
as the parent drug in one model of anxiolytic activity.
Buspirone is excreted mainly as metabolites in the urine,
and also the faeces.
