Table 1.
H3 recepor ligands and the mechanisms entailed in their antiepileptic effect in diverse models of epilepsy
| H3 receptor ligands | Model used | Effect observed | Mechanism | Reference |
|---|---|---|---|---|
| Thioperamide (3.75, 7.5 and 15 mg·kg−1 i.p.) | MES seizure in mice | ↓ Duration of each phase of convulsion | H3 antagonism/inverse agonism: reversal of auto-inhibitory HA synthesis and release; H1-mediated seizure inhibition | Yokoyama et al., 1993c |
| Clobenpropit (0.1, 0.3, 1 and 3 mg·kg−1 i.p.) | MES seizure in mice | ↓ Duration of each phase of convulsion | As first mechanism; ↑ HDC activity | Yokoyama et al., 1994 |
| AQ-0145 | MES seizure in mice | ↓ Duration of each phase of convulsion | As first mechanism | Murakami et al., 1995 |
| Thioperamide (7.5 and 15 mg·kg−1 i.p.) | Proconvulsive effect of theophylline on MES seizure in mice | ↓ Mortality | As first mechanism | Yokoyama et al., 1997 |
| Clobenpropit (20–40 mg·kg−1 i.p.) | MES- and PTZ-induced seizure in mice | ↑ Threshold for tonic seizure in MES test ⊗ PTZ seizure threshold | As first mechanism; pharmacokinetic synergism with AEDs | Fischer and van der Goot, 1998 |
| Thioperamide (5–10 mg·kg−1 i.p.) and Clobenpropit (1, 5, 10 and 50 µg i.c.v.) | Amygdaloid kindled (electrically) rats | ↓ Seizure stage; ↓ AD duration | As first mechanism | Kakinoki et al., 1998 |
| Clobenpropit (0.5, 2, 5, and 10 mg·kg−1 i.p.) | Amygdaloid kindled (electrically) rats | ↓ Seizure stage; ↓ AD duration | As first mechanism; interaction with GABA actions | Ishizawa et al., 2000 |
| Thioperamide (3.75, 7.5 and 15 mg·kg−1 i.p.) R-α-methylhistamine (10 µg i.c.v.) | PTZ-induced seizure in mice | ↑ Latency of myoclonic jerks & clonic generalized seizures; ↓ % incidence; H3 agonism reversed the above | As first mechanism; | Vohora et al., 2000 |
| Thioperamide and AQ 0145 (each 5 and 10 mg·kg−1 i.p. and 10–50 µg i.c.v.) | Amygdaloid kindled (electrically) rats | ↓ Seizure stage; ↓ AD duration | As first mechanism | Kamei, 2001 |
| Thioperamide (3.75–7.5 mg·kg−1 i.p.); R-α-methylhistamine (10 µg i.c.v.) | MES- and PTZ-induced seizure in mice | ↑ Latency of myoclonic jerks and clonic generalized seizures; ↓ Duration of tonic and clonic phases; H3 agonism reversed the above | As first mechanism; potentiation of AEDs | Vohora et al., 2001 |
| Thioperamide (5, 10 and 20 µg; i.c.v.) | PTZ-induced kindling in rats | ↓ Duration of each phase of convulsion; ↑ seizure threshold | As first mechanism | Chen et al., 2002 |
| Clobenpropit (10 and 20 µg i.c.v.) Immepip (5 and 10 µg i.c.v.) | PTZ-induced kindling in rats | Delayed onset of kindling; ↑ latency of seizure stage; H3 agonism reversed the above | As first mechanism | Zhang et al., 2003a,b |
| Carcinine and Thioperamide (each 2–20 mg·kg−1 i.p.) | PTZ induced kindling in mice | ↑ Latency of seizures; ↓ Seizure stages | ↑ HDC activity; ↑ HA release | Chen et al., 2004 |
| Iodophenpropit, Clobenpropit, Thioperamide (each 10 mg·kg−1 i.p./i.c.v.), AQ0145 (20 mg·kg−1 i.p.); VUF5514, VUF5515 VUF4929 (i.c.v.) | Amygdaloid kindled (electrically) rats; MES seizure in rats | ↓ Seizure stages; ↓ AD duration; ↓ tonic seizure ⊗ Duration of clonic phase | As first mechanism | Harada et al., 2004a,b |
| Thioperamide (25 mg·kg−1 i.p.) | EL mice (model of human TLE) | ↑ Latency; ↓ % of seizure incidence | ↑ HDC activity; ↑ Brain HA release | Yawata et al., 2004 |
| Clobenpropit (i.c.v.) | PTZ-induced kindling in mice | ↑ Latency of myoclonic jerks and clonic generalized seizures; ↓ Seizure stages | As first mechanism | Zhang et al., 2004 |
| Thioperamide (10, 20 and 50 µg i.c.v.) | Imipramine-induced seizures in amygdaloid kindle (electrically) rats | ↓ Behavioural seizure; ↓ EEG seizure | As first mechanism | Ago et al., 2006 |
| Clobenpropit (0.75 and 1.5 mg·kg−1 i.p.) | MES seizure in mice | Inhibition of seizure | Pharmacodynamic synergism with pyridoxine | Uma Devi et al., 2011 |
| Thioperamide (2–10 mg·kg−1 i.p.) and R-α-methylhistamine (10–40 mg·kg−1 i.p.) | MES and PTZ induced seizure in mice | ⊗ Seizure threshold in both model | H3 antagonism and agonism | Scherkl et al., 1991 |
| Thioperamide and Burimamide | Picrotoxin induced seizure | ↑ Severity of clonic convulsions | H3 antagonism | Sturman et al., 1994 |
| Thiopermide (20 and 30 mg·kg−1 i.p.) Betahistine (200 and 400 mg·kg−1 i.p.) | Amygdaloid kindled rats | No anticonvulsive effect; mild effect only at very high dose | H3 antagonism | Yoshida et al., 2000 |
| Thioperamide (15 mg·kg−1 i.p.) | Methionine-sulfoximine induced convulsion in mice | ⊗ Seizure latency and mortality | H3 antagonism | Vohora et al., 2010 |
AD, after discharge; MES, Maximal electroshock; PTZ, pentylenetetrazole; ↑ increase; ↓ decrease; ⊗ no change.