Aminergic receptors

Table 7.4. Changes in cholinergic and aminergic receptors in depression and following antidepressant treatment...

Del Olmo E, Pazos A (2001) Aminergic receptors during the development of the human brain the contribution of in vitro imaging techniques. J Chem Neuroanat 22 101-114... 

Aripiprazole is an arylpiperazine quinolinone derivative that has complex functional activity at several aminergic receptors currently thought to be important in the pathophysiology and pharmacotherapy of schizophrenia, including dopamine D2 and serotonin 5-HTia and 5-HT2A/C receptors. The affinity of aripiprazole for D2 receptors is relatively high however, it has a low propensity to cause untoward extrapyramidai symptoms and hyperprolactinemia (58). 

Histamine receptors were first divided into two subclasses Hi and H2 by Ash and Schild (1966) on the basis that the then known antihistamines did not inhibit histamine-induced gastric acid secretion. The justification for this subdivision was established some years later when Black (see Black et al. 1972) developed drugs, like cimetidine, that affected only the histamine stimulation of gastric acid secretion and had such a dramatic impact on the treatment of peptic ulcers. A recently developed H2 antagonist zolantidine is the first, however, to show significant brain penetration. A further H3 receptor has now been established. It is predominantly an autoreceptor on histamine nerves but is also found on the terminals of aminergic, cholinergic and peptide neurons. All three receptors are G-protein-coupled but little is known of the intracellular pathway linked to the H3 receptor and unlike Hi and H2 receptors it still remains to be cloned. Activation of Hi receptors stimulates IP3 formation while the H2 receptor is linked to activation of adenylate cyclase. 

Shi, L. and Javitch, J. A. (2002) The binding site of aminergic G protein-coupled receptors. Annu. Rev. Pharmacol. Toxicol. 42,437 467. 

The interaction of glutamate and its NMDA receptor with other brain neurotransmitters, including the aminergic dopamine and serotonin neuromodulators which are the main focus of this book, is very complex and only a few, simplified accounts of how NMDA receptor hypofunction... 

In conclusion, the distribution of H3 receptors and the effects of lesions are consistent with functional studies showing that they are inhibitory receptors not only on histaminergic nerve terminals, but also on various aminergic and non-aminergic cerebral neurons and therefore they may be involved in a large variety of functions. 

As mentioned above, the existence of H3 receptors located presynaptically as heteroreceptors on other aminergic neurons, such as serotonergic, noradrenergic and dopaminergic neurons has been suggested [10-13], However, in a series of experiments we found that neither RmHA nor THIOP affected the ACTH response to serotonergic activation induced by administration of the 5-HT precursor 5-hydroxytryptophan in combination with the 5-HT re-uptake inhibitor fluoxetine [27],... 

The available data indicate that systemic administration of H3 receptor agonists oppose the stimulatory effect of endogenous HA on PRL secretion and that this effect, which is prevented by concomitant blockade of the H3 receptors, occurs on presynaptic histaminergic neurons rather than on other aminergic neurons. At least, the effect is not exerted via activation of H3 heteroreceptors on serotonergic neurons. 

However, receptor autoradiography and in vitro studies have suggested that H3 receptors are located on other aminergic neurons in the brain. Since amines such as serotonin and catecholamines are involved in the regulation of pituitary hormone secretion, it is obvious that an action of the H3 receptor compounds may be exerted via these H3 heteroreceptors. Only few studies have evaluated this heteroreceptor action. It has been excluded that the effect of the H3 receptor agonists is due to an effect on H3 receptors located on serotonergic neurons, while an effect on catecholaminergic neurons has yet not been excluded. 

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