Abstract
Objective: Despite a large number of studies have been reported that
L-type voltage dependent calcium channel (VDCC) blockers have
anticonvulsant properties, in the vast majority of these experimental
studies, VDCC blockers have given through systemic but not central
routes of administration. The discrepancies of the anticonvulsant role
of VDCC blockers may be due to a potential confounding
cardiovascular effect of VDCC blockers, in pretended central action
following their systemic administration. In an attempt to clarify such
criticism, we examined the effects of three different VDCC blockers
such as amlodipine, verapamil and diltiazem on pentylenetetrazole
(PTZ)-induced seizures after their systemic intraperitoneal (ip)
administration and compared these results with those obtained after
their intracerebroventricular (icv) administration in mice.

Methods: Adult male Swiss-Webster mice were used in the study.
After 50 min and 30 min following ip and icv. administrations of
VDCCBs, respectively, each mouse received a single subcutaneous
(sc) injection of 85mg/kg of PTZ and was monitored continuously for
30 min for the appearance of clonic convulsions. The latency of the
on-set time of clonic seizures was also recorded.

Results: Ip administration of amlodipine (3 and 5 mg/kg), verapamil
and diltiazem (30 and 50 mg/kg) significantly prolonged on-set time
of the PTZ-induced seizures. By contrast, icv administration of
amlodipine, verapamil and diltiazem (10, 30 and 80mg) had no
significant effect on the on-set time of the seizures.

Conclusions: Our results suggest that systemic administered VDCC
blockers possess anticonvulsant activity on PTZ-induced seizures.
However, lack of anticonvulsant effect of centrally administered L-type
VDCC blockers on PTZ-induced seizures indicates that they modulate
PTZ-induced seizures by a peripheral, rather than a central mode of
action.

Key words: amlodipine, diltiazem, epilepsy, calcium channel, pentylenetetrazole, seizure, mice