Neuroleptics adrenergic receptors

The actions of neuroleptics on histamine, muscarinic and alpha] adrenergic receptors explain the side effects of these drugs, i.e. sedation, anticholinergic effects and hypotensive effects, respectively, which are generally considered to be undesirable and can lead to poor patient compliance. Table 11.9 summarises the main side effects of the typical neuroleptics. 

Other effects Blockade of a-adrenergic receptors causes orthostatic hypotension and lightheadedness. The neuroleptics also alter temperature-regulating mechanisms and can produce poik-ilothermia (body temperature varies with the environment). In the pituitary, neuroleptics block D2 receptors, leading to an increase in prolactin release. 

Other effects Drowsiness occurs due to CNS depression, usually during the first 2 weeks of treatment. Confusion is sometimes encountered.The neuroleptics often produce dry mouth, urinary retention, constipation, and loss of accommodation. They block a-adrenergic receptors, resulting in lowered blood pressure and orthostatic hypotension. The neuroleptics depress the hypothalamus, causing amenorrhea, galactorrhea, infertility, and impotence. 

Peroutka, S.J. and Snyder, S.H. (1980) Relationship of neuroleptic drug effects at brain dopamine, serotonin, a-adrenergic, and histamine receptors to clinical potency. Am Psychiatry 137 1518-1522. 

Remoxipride is a selective D2 antagonist with higher affinity for the D2S subtype of receptors. It has no affinity for 5-HT, adrenergic, muscarinic or histamine receptors but, unlike the other atypical neuroleptics, does bind to sigma receptors (see p. 453 for possible importance of sigma receptors). 

Despite the preponderance of data correlating the dopamine D2 receptor with schizophrenia, alternative sites in the brain (serotonergic, adrenergic, glutamatergic, and GABAergic) are also being investigated to explain the actions of atypical neuroleptics. 

The antipsychotic actions of neuroleptic drugs reflect blockade at dopamine and/or serotonin receptors. However, many of these agents also block cholinergic, adrenergic, and histamine receptors, causing a variety of side effects (Figure 13.3). 

Neuroleptic drugs block at dopaminergic and serotonergic receptors as well as at adrenergic, cholinergic, and histamine-binding receptors. GABA = y-aminobutyric acid. 

The phenothiazines inhibit dopaminergic receptors in the CNS, a property thought to account for their neuroleptic effect. In addition, phenothiazines inhibit muscarinic, a-adrenergic, histaminic, and serotonergic receptors, which accounts for many of their toxic or undesirable side effects. 

Neuroleptic Interactions with the Noradrenergic q-Receptor - Autonomic sympatholytic effects such as orthostatic hypotension and sedation are among the most prominent untoward actions of neuroleptic drugs. These side effects have been attributed to blockade of central and peripheral adrenergic a-receptors39 0 1 but direct quantitative evaluation of a-receptor blockade in the CNS by these agents has not been heretofore feasible. In... 

---