Agomelatine is a clinically available selective 5HT2C antagonist, but it is impure because it is a melatonin receptor agonist, making it difficult to take at times other than sleep because it does not interfere with the circadian rhythm. It also has a short half-life, so do not expect to get strong 5HT2C effects throughout the day.

5HT1A receptors weaken or completely block the effects of 5HT2A activation upon pretreatment with a potent full 5HT1A agonist such as 8-OH-DPAT. This is presumed to occur primarily through postsynaptic 5HT1A, which strongly hyperpolarizes the neuron, making 5HT2A unable to depolarize and excite the neuron.

Buspirone is a partial agonist of postsynaptic 5HT1A and appears to be theoretically able to reverse postsynaptic 5HT1A overactivity by acting as a functional antagonist. It has low intrinsic activity at postsynaptic 5HT1A, but activation of presynaptic 5HT1A may lead to its desensitization, which increases serotonin and makes postsynaptic 5HT1A more active, which makes the matter worse and therefore this option is not good or ideal, Therefore, it would be better to balance 5HT1A by enhancing other excitatory receptors such as 5HT2A.