Buspirone drug administration

These observations question the role of noradrenaline as an initiator of anxiety as does the finding that the anti-anxiety drug, buspirone (see Chapter 9), increases the concentration of noradrenaline in the extracellular fluid in the frontal cortex of freely-moving rats (Done and Sharp 1994). Whether this is because buspirone is metabolised to l-(2-pyrimidinyl)-piperazine (1-PP), which is an a2-adrenoceptor antagonist, is uncertain. Unfortunately, no studies have investigated the effects of chronic administration of this drug on noradrenergic transmission this could be important because, unlike benzodiazepines, buspirone is effective therapeutically only after several weeks of treatment. 

Absolute bioavailability this implies a comparison of plasma levels after oral and i.v. administration of the drug. Most psychotropic drugs have a good bioavailability, i.e. values between 30 and 100%. Low bioavailabilitv, as seen with buspirone, is associated with highly variable drug plasma concentrations and is not a desirable feature of a drug... 

Other drugs of the depressant, antianxiety, antipyschotic, and anticonvulsive types are being investigated as treatments for cocaine abuse. Those which have been or will be covered in this course include the heterocyclic antidepressants desipramine and imipramine, which diminish cocaine use and craving as well as improve the outcome in the first few months of treatment. Buprenorphine (depressant) may augment the reward system (it has been found to suppress self-administration of cocaine in monkeys). Lithium sometimes works for those who are clinically depressives. Carbamazapine, bromocriptine and mazindol are also used as well as fluphenthixol and buspirone. 

VanderMaelen CP, Matheson GK, Wilderman RC, Patterson LA. Inhibition of serotonergic dorsal raphe neurons by systemic and iontophoretic administration of buspirone, a non-benzodiazepine anxiolytic drug. Eur J Pharmacol 1986 129 123-130. 

Co-administration of erythromycin with the anxiolytic drug buspirone increased the plasma concentration of buspirone (25). 

The drug is rapidly absorbed after oral administration, and peak plasma concentrations occnr abont 1 honr later. Buspirone is extensively metabolized, with less than 1% of an administered dose excreted nnchanged. Important rontes of biotransformation are hydroxylation and oxidative dealkylation, the latter yielding l-(2-pyrimidinyl) piperazines. This metabolite has been shown to concentrate in the brain and to have pharmacologic activity, thongh its capacity to interact with different brain receptors appears to differ from that of buspirone. 

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