Autoreceptors buspirone effects

With regard to generalized anxiety disorder, it has been postulated that an overactivity of the stimulatory 5-HT pathways occurs. Drugs such as buspirone and ipsapirone are effective in such conditions because they stimulate the inhibitory S-HT a autoreceptors on the raphe nuclei and thereby reduce serotonergic function. It is noteworthy that the SSRIs often worsen anxiety initially because they temporarily enhance serotonergic function. Adaptive changes in the pre- and postsynaptic 5-HT receptors then occur leading to a reduction in the anxiety state. 

Buspirone acts as an agonist of somatodendritic 5-HTja autoreceptors, and has variable antagonistic effects on postsynaptic 5-HTja receptors (Jann, 1988 Baldessarini, 1996 Chouinard et ah, 1999). It also causes down-regulation of d-HTj receptors (Cole and Yonkers, 1995). 

FIGURE 7—33. Mechanism of action of buspirone augmentation—pact 3. Shown here is how buspirone potentiates ineffective SSRI action at 5HT1A somatodendritic autoreceptors, resulting in the desired disinhibition of the 5HT neuron. This combination of 5HT1A agonists plus SSRIs may be more effective, not only in depression but also in other disorders treated by SSRIs, such as obsessive-compulsive disorder and panic. 

FIGURE 8—11. Serotonin 1A partial agonists such as buspirone may reduce anxiety by actions both at presynaptic somatodendritic autoreceptors (left) and at postsynaptic receptors (right). Presynaptic actions are more likely related to anxiolytic actions, and postsynaptic actions are perhaps more likely linked to side effects such as nausea and dizziness. 

Several clinical studies have shown buspirone (14a) to have anxiolytic efficacy equivalent to that of DZ with significantly less sedation. ° Rats trained to discriminate oxazepam or pentobarbital from vehicle did not generalize to buspirone. At doses above those which are anxiolytically relevant in man, the drug caused a dose-related elevation of plasma prolactin in male subjects, and like the BZ s also increased growth hormone levels. Buspirone elicits a dose-dependent rise in rat striatal dopamine (DA) metabolite levels and may do so by selective antagonism of presynaptic DA autoreceptors with minimal postsynaptic effects. Its catalepsy-reversal effects may occur... 

Peng et al. showed using two different models of experimental anxiety that high doses of berberine (100, 500 mg/kg) have anxiolytic effect, which was similar to that observed with 1 mg/kg diazepam and 2 mg/kg buspirone. They concluded that this effect might be related to the enhancement of turnover rates of monoamines in the brain stem and the reduction of serotonergic system activity. Moreover, berberine was able to reduce serotonergic system activity by regulating the activity of somatodendritic 5-HTlA autoreceptors and postsynaptic 5-HTlA and 5-HT2 receptors [71]. 

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