Low-potency first-generation antipsychotics cause more side effects due to which receptor block?

Low-potency first-generation antipsychotics cause more side effects due to which receptor block?

• A. Histamine Blockade
• B. Dopamine D2 Blockade
• C. Serotonin Blockade
• D. NMDA Blockade

Answer: (A)

Low-potency first-generation antipsychotics tend to block multiple receptors beyond dopamine D2, and the extent of non-dopaminergic blockade drives their broader side-effect profile. Histamine H1 blockade is a key contributor to the prominent sedation, weight gain, and fatigue seen with these drugs. While D2 blockade underlies therapeutic effects and some motor side effects, it's the off-target H1 (and other non-dopaminergic) receptor blockade that explains why low-potency agents produce more overall side effects. Among the listed options, histamine blockade best accounts for these non-dopaminergic adverse effects.

Low-potency first-generation antipsychotics tend to block multiple receptors beyond dopamine D2, and the extent of non-dopaminergic blockade drives their broader side-effect profile. Histamine H1 blockade is a key contributor to the prominent sedation, weight gain, and fatigue seen with these drugs. While D2 blockade underlies therapeutic effects and some motor side effects, it's the off-target H1 (and other non-dopaminergic) receptor blockade that explains why low-potency agents produce more overall side effects. Among the listed options, histamine blockade best accounts for these non-dopaminergic adverse effects.