Histamine antipsychotic drugs

Kroeze, W. K., Hufeisen, S. J., Popadak, B. A. et al. HI-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. Neuropsychopharmacology 28 519-526, 2003. 

Kim, S.F., Huang, A.S., Snowman, A.M., Teuscher, C. and Snyder, S.H. (2007) From the coven Antipsychotic drug-induced weight gain mediated by histamine HI receptor-linked activation of hypothalamic AMP-kinase. Proceedings of the National Academy of Sciences of the United States of America, 104 (9), 3456-3459. 

The first phenothiazine antipsychotic drugs, with chlorpromazine as the prototype, proved to have a wide variety of central nervous system, autonomic, and endocrine effects. Although efficacy of these drugs is primarily driven by D2-receptor blockade, their adverse actions were traced to blocking effects at a wide range of receptors including a adrenoceptors and muscarinic, Hi histaminic, and 5-HT2 receptors. 

FIGURE 11—7. This figure represents an icon of a conventional antipsychotic drug. Such drugs generally have at least four actions blockade of dopamine 2 receptors (D2) blockade of muscarinic-cholinergic receptors (Ml) blockade of alpha 1 adrenergic receptors (alpha 1) and blockade of histamine receptors (antihistaminic actions [HI ). 

Still other pharmacologic actions are associated with the conventional antipsychotic drugs. These include generally undesired activity at alpha 1 adrenergic receptors as well as at histamine 1 receptors, as already discussed (Fig. 11—7). Thus, conventional antipsychotic drugs have activities at three of the same neurotransmitter receptors... 

FIGURE 11 — 12. Side effects of conventional antipsycbotics, part 2. In this diagram, the icon of a conventional antipsychotic drug is shown with its HI (antihistamine) portion inserted into histamine receptors, causing the side effects of weight gain and drowsiness. 

Many of the side effects associated with antipsychotic agents can be attributed to their antagonist activity at a variety of CNS receptors, which include histamine Hi, adrenergic 01/02, cholinergic Mi receptors, serotonin 5-HT2, and dopamine D2 receptors in the brain. For example, antipsychotic drug side effects such as sedation. 

Besides weight gain, probably the most common side effect from antipsychotics in young people is sedation. Histamine receptor blockade appears to mediate this side effect. Excessive sleepiness can interfere with a youth s academic performance, cause sluggishness, and cause a child to appear drugged to their peers and family. 

The tertiary members of these classes (Figure 8-2) are often used for their effects on the eye or the central nervous system. Many antihistaminic (see Chapter 16 Histamine, Serotonin, the Ergot Alkaloids), antipsychotic (see Chapter 29 Antipsychotic Agents Lithium), and antidepressant (see Chapter 30 Antidepressant Agents) drugs have similar structures and, predictably, significant antimuscarinic effects. 

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