Clozapine: Selective Labeling of Sites Resembling 5HT6 Serotonin Receptors May Reflect Psychoactive Profile

Table 4 Comparison of drug affinities at [ ³ H]clozapine binding sites in rat brain and cloned serotonin receptors

Ligand	5HT_1a^a,b (nM)	5HT_1B^c,d,e (nM)	5HT_1C^f (nM)	5HT_1E^g,h (nM)	5HT_1Fⁱ (nM)	5HT₂^j (nM)	5HT_5A^k (nM)	5HT_5B^k (nM)	5HT₇^l,m,n (nM)	[³H]Clozapine (nM)
8-OH DPAT	0.06	>10,000	—	—	>1,000	>1,000	>10,0	398	35–52	5,000
5HT	0.27–1.66	16–48	—	8.14	70–125	250	251	251	0.6–1.8	200,000
Spiperone	63–134	>10,000	957	—	9.9–20	0.5	—	—	9.9–20	24.6
Mesulergine	400	—	3.0	>1,000	>1,000	—	—	—	21.1	1,000
Methysergide	—	436–1,823	—	300	6.3–14	1.0–5.0	63	126	13.4	8.2
Ketanserin	2,100–23,000	>10,000	28.5	—	3,162	1.0–5.0	>10,000	1,584	265–37,500	81.9
Ritanserin	—	—	2.7	—	—	0.2	—	—	15	123
Methiothepin	—	13	—	6.7	>1,000	0.4	700	15.8	0.3–8.8	9.8
Ergotamine	—	—	—	600	50–55	—	3.9	3.2	—	9.1
Sumatriptan	—	465	—	2,300	67–79	—	3.9	3.2	1,000	>1,000
Clozapine	—	4.2	7.2	—	—	5.0	—	—	4.0	5.3

All numbers represent K_i values from the literature as noted or [³H]clozapine binding to rat brain membranes. Drug affinities for [³H]clozapine binding sites are mean values of two to three determinations varying less than 20%.
^aFargin et al. (19)
^bAlbert et al. (20)
^cMaroteaux et al. (21)
^dAdham et al. (22)
^eVoigt et al. (23)
^fRoth et al. (24)
^gZgombick et al. (25)
^hMcAllister et al. (26)
ⁱAmlaiky et al. (27)
^jMeltzer et al. (28)
^kMatthes et al. (29)
^lRoth et al. (30)
^mRuat et al. (31)
ⁿShen et al. (32)

ISSN: 1528-3658