NBME 18 Answers ↦
M1 receptors are for sure the major muscarinic receptor type found in the CNS, but M3 receptors are the muscarinic subtype involved in vomiting controlled by the CNS. This is definitely a random fact, but I think they also wanted you to eliminate all other options. Targeting the sympathetic system (options A and B) won't make a difference. NMDA receptors are a major receptor throughout the CNS, but they're not a target of antihistamines, and neither are serotonin receptors. We know that antihistamines target histamine and muscarinic receptors, but the H2 histamine receptor is responsible for gastrin secretion in the stomach, so the answer must be antagonism of M3 receptors.
^ First generation antihistamines definitely antagonize serotonin receptors within the CNS, which can cause weight gain and increase appetite. However, this plays little role in motion sickness.
That is confusing because scopolamine (anti-muscarinic used to treat motion sickness) is an M1 receptor antagonist
"As we know that all mAChR subtypes are expressed in
the brain, while only M1, M2, and M5 exist in vestibular ganglia
and vestibular end organs in humans . The M1, M3, and M5
are postsynaptic excitatory receptors; M2 and M4 receptors are
inhibitory. Furthermore, selective M3 and M5 antagonist zamifenacin was found to be as effective as scopolamine in preventing Motion Sickness. These lines of evidence suggest that scopolamine might exert its antagonistic effect on peripheral M1 and M5 and/or central M1 and M3 mAChR to prevent MS"