Role of 5-HT_2A receptor antagonists in the treatment of insomnia

Figures & data

Figure 1 Chemical structures of 5-HT_2A receptor antagonists.

Table 1 Relative binding affinities for selective 5-HT_2A receptor antagonists. Potency values are expressed as pK_i, K_i (nM) or IC₅₀ (nM) as noted

	5-HT2A	5-HT2C	Development status
Ritanserin	pKi 10.08a	pKi 9.36a	Discontinued
	pKi 8.88b	pKi 7.61b
Eplivanserin	pKi 10.34a	pKi 8.87a	Discontinued
	pKi 9.40b	pKi 6.13b
Volinanserin	pKi 10.52a	pKi 8.42a	Discontinued
	pKi 9.76b	pKi 6.35b
	IC50 0.3c
	IC50 0.39d	IC50 36d
Pimavanserin	pKi 9.3a	pKi 8.80a	Phase III clinical development for indications other than insomnia
	pKi 9.7b	pKi 8.00b
Nelotanserin	Ki 2.3c	Ki 221c	Discontinued
	Ki 0.4d	Ki 106d
Pruvanserin	IC50 1.0c		Discontinued
	IC50 0.35d	IC50 1334d

Notes:

a Membrane binding pK_i;¹⁴

b whole cell binding pK_i;¹⁴

c cloned rat receptor;^33,39,77

d cloned human receptor.^39,77

Table 2 Positive effects on sleep and side effects common to 5-HT_2A receptor antagonists

5-HT2A receptor antagonism
Positive effects on sleep	Side effects
Increased deep slow wave sleep	Dizziness/hypotension
Decreased wake after sleep onset	Fatigue
Decreased number of arousals/awakenings	Headache
Improved sleep maintenance	Nausea/vomiting
Improved sleep efficiency	Constipation

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