PHARMACOLOGY OF NIMODIPINE
INTRODUCTION
Nimodipine, sold under the brand name Nimotop among others, is a calcium channel blocker
used in preventing vasospasm secondary to subarachnoid hemorrhage (a form of cerebral
hemorrhage). It was originally developed within the calcium channel blocker class as it was used
for the treatment of high blood pressure, but is not used for this indication.
Nimodipine is a dihydropyridine. Dihydropyridines are a type of calcium channel blocker (CCB),
which refer to a group of medications that block calcium channels located in the muscle cells of
the heart and arterial blood vessels, thereby reducing the entry of calcium ions into the cell. By
blocking these channels, CCBs promote blood vessel dilation (i.e. vasodilation), as well as
changes in heart function, including reductions in heart rate, strength of contractility, and speed
of conduction within the heart. Overall, these effects contribute to a drop in blood pressure and a
decrease in the oxygen requirements of the heart. Because of these cardiovascular effects, CCBs
can be used to treat hypertension(high blood pressure), among other heart problems, including
angina (chest pain that results from a compromised oxygen supply to the heart muscle) and
cardiac arrhythmias (disturbances in the heart rhythm).
Nimodipine is a calcium channel blocker used to improve neurological outcomes in patients
with subarachnoid hemorrhage due to a ruptured intracranial aneurysm. Nimodipine is a 1,4-
dihydropyridine calcium channel blocker. It acts primarily on vascular smooth muscle cells by
stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting
the influx of calcium in smooth muscle cells, nimodipine prevents calcium-dependent smooth
muscle contraction and subsequent vasoconstriction. Compared to other calcium channel
blocking agents, nimodipine exhibits greater effects on cerebral circulation than on
peripheral circulation. Nimodipine is used to as an adjunct to improve the neurologic outcome
following subarachnoid hemorrhage from ruptured intracranial aneurysm.
� Subarachnoid hemorrhage (SAH) is bleeding into the subarachnoid space—the area
between the arachnoid membrane and the pia mater surrounding the brain. It is the bleeding in
the space between the brain and the tissue covering the brain. Symptoms may include a severe
headache of rapid onset, vomiting, decreased level of consciousness, fever, and sometimes
seizures.
� An aneurysm is a bulge in a blood vessel caused by a weakness in the blood vessel wall,
usually where it branches. As blood passes through the weakened blood vessel, the blood
pressure causes a small area to bulge outwards like a balloon.
MECHANISM OF ACTION
Although the precise mechanism of action is not known, nimodipine blocks intracellular influx
of calcium through voltage-dependent and receptor-operated slow calcium channels across the
, membranes of myocardial, vascular smooth muscle, and neuronal cells. By specifically binding
to L-type voltage-gated calcium channels, nimodipine inhibits the calcium ion transfer, resulting
in the inhibition of vascular smooth muscle contraction. Evidence suggests that the dilation of
small cerebral resistance vessels, with a resultant increase in collateral circulation, and/or a direct
effect involving the prevention of calcium overload in neurons may be responsible for
nimodipine's clinical effect in patients with subarachnoid hemorrhage.
Dihydropyridines work by binding to and blocking voltage-gated L-type calcium channels found
on smooth muscle cells of arterial blood vessels. Usually, these channels open in response to an
electrical signal, or action potential, hence the name “voltage-gated” L-type calcium channels.
These calcium channels are responsible for regulating the entry of extracellular calcium into
muscle cells, which in turn stimulates muscular contraction of blood vessels. By blocking these
channels, dihydropyridines are able to decrease blood vessel contraction, leading to a sustained
vasodilation. In turn, vasodilation reduces vascular resistance of arterial blood vessels, leading to
a drop in blood pressure.
PHARMACOKINETICS
In humans, nimodipine is rapidly absorbed after oral administration, and peak concentrations are
generally attained within one hour. The terminal elimination half-life is approximately 8 to 9
hours but earlier elimination rates are much more rapid, equivalent to a half-life of 1-2 hours; a
consequence is the need for frequent (every 4 hours) dosing. There were no signs of
accumulation when nimodipine was given three times a day for seven days. Nimodipine is over
95% bound to plasma proteins. The binding was concentration independent over the range of 10
ng/mL to 10 mcg/mL. Nimodipine is eliminated almost exclusively in the form of metabolites
and less than 1% is recovered in the urine as unchanged drug. Numerous metabolites, all of
which are either inactive or considerably less active than the parent compound, have been
identified. The metabolism of nimodipine is mediated by CYP3A4. Because of a high first-pass
metabolism, the bioavailability of nimodipine averages 13% after oral administration.
� Plasma protein binding refers to the degree to which medications attach to proteins within
the blood. A drug's efficiency may be affected by the degree to which it binds. The less bound a
drug is, the more efficiently it can traverse cell membranes or diffuse. Common blood proteins
that drugs bind to are human serum albumin, lipoprotein, glycoprotein, and α, β‚ and γ globulins.
Food Effects
In a study of 24 healthy male volunteers, administration of nimodipine capsules following a
standard breakfast resulted in a 68% lower peak plasma concentration and 38% lower
bioavailability relative to dosing under fasted conditions.
INTRODUCTION
Nimodipine, sold under the brand name Nimotop among others, is a calcium channel blocker
used in preventing vasospasm secondary to subarachnoid hemorrhage (a form of cerebral
hemorrhage). It was originally developed within the calcium channel blocker class as it was used
for the treatment of high blood pressure, but is not used for this indication.
Nimodipine is a dihydropyridine. Dihydropyridines are a type of calcium channel blocker (CCB),
which refer to a group of medications that block calcium channels located in the muscle cells of
the heart and arterial blood vessels, thereby reducing the entry of calcium ions into the cell. By
blocking these channels, CCBs promote blood vessel dilation (i.e. vasodilation), as well as
changes in heart function, including reductions in heart rate, strength of contractility, and speed
of conduction within the heart. Overall, these effects contribute to a drop in blood pressure and a
decrease in the oxygen requirements of the heart. Because of these cardiovascular effects, CCBs
can be used to treat hypertension(high blood pressure), among other heart problems, including
angina (chest pain that results from a compromised oxygen supply to the heart muscle) and
cardiac arrhythmias (disturbances in the heart rhythm).
Nimodipine is a calcium channel blocker used to improve neurological outcomes in patients
with subarachnoid hemorrhage due to a ruptured intracranial aneurysm. Nimodipine is a 1,4-
dihydropyridine calcium channel blocker. It acts primarily on vascular smooth muscle cells by
stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting
the influx of calcium in smooth muscle cells, nimodipine prevents calcium-dependent smooth
muscle contraction and subsequent vasoconstriction. Compared to other calcium channel
blocking agents, nimodipine exhibits greater effects on cerebral circulation than on
peripheral circulation. Nimodipine is used to as an adjunct to improve the neurologic outcome
following subarachnoid hemorrhage from ruptured intracranial aneurysm.
� Subarachnoid hemorrhage (SAH) is bleeding into the subarachnoid space—the area
between the arachnoid membrane and the pia mater surrounding the brain. It is the bleeding in
the space between the brain and the tissue covering the brain. Symptoms may include a severe
headache of rapid onset, vomiting, decreased level of consciousness, fever, and sometimes
seizures.
� An aneurysm is a bulge in a blood vessel caused by a weakness in the blood vessel wall,
usually where it branches. As blood passes through the weakened blood vessel, the blood
pressure causes a small area to bulge outwards like a balloon.
MECHANISM OF ACTION
Although the precise mechanism of action is not known, nimodipine blocks intracellular influx
of calcium through voltage-dependent and receptor-operated slow calcium channels across the
, membranes of myocardial, vascular smooth muscle, and neuronal cells. By specifically binding
to L-type voltage-gated calcium channels, nimodipine inhibits the calcium ion transfer, resulting
in the inhibition of vascular smooth muscle contraction. Evidence suggests that the dilation of
small cerebral resistance vessels, with a resultant increase in collateral circulation, and/or a direct
effect involving the prevention of calcium overload in neurons may be responsible for
nimodipine's clinical effect in patients with subarachnoid hemorrhage.
Dihydropyridines work by binding to and blocking voltage-gated L-type calcium channels found
on smooth muscle cells of arterial blood vessels. Usually, these channels open in response to an
electrical signal, or action potential, hence the name “voltage-gated” L-type calcium channels.
These calcium channels are responsible for regulating the entry of extracellular calcium into
muscle cells, which in turn stimulates muscular contraction of blood vessels. By blocking these
channels, dihydropyridines are able to decrease blood vessel contraction, leading to a sustained
vasodilation. In turn, vasodilation reduces vascular resistance of arterial blood vessels, leading to
a drop in blood pressure.
PHARMACOKINETICS
In humans, nimodipine is rapidly absorbed after oral administration, and peak concentrations are
generally attained within one hour. The terminal elimination half-life is approximately 8 to 9
hours but earlier elimination rates are much more rapid, equivalent to a half-life of 1-2 hours; a
consequence is the need for frequent (every 4 hours) dosing. There were no signs of
accumulation when nimodipine was given three times a day for seven days. Nimodipine is over
95% bound to plasma proteins. The binding was concentration independent over the range of 10
ng/mL to 10 mcg/mL. Nimodipine is eliminated almost exclusively in the form of metabolites
and less than 1% is recovered in the urine as unchanged drug. Numerous metabolites, all of
which are either inactive or considerably less active than the parent compound, have been
identified. The metabolism of nimodipine is mediated by CYP3A4. Because of a high first-pass
metabolism, the bioavailability of nimodipine averages 13% after oral administration.
� Plasma protein binding refers to the degree to which medications attach to proteins within
the blood. A drug's efficiency may be affected by the degree to which it binds. The less bound a
drug is, the more efficiently it can traverse cell membranes or diffuse. Common blood proteins
that drugs bind to are human serum albumin, lipoprotein, glycoprotein, and α, β‚ and γ globulins.
Food Effects
In a study of 24 healthy male volunteers, administration of nimodipine capsules following a
standard breakfast resulted in a 68% lower peak plasma concentration and 38% lower
bioavailability relative to dosing under fasted conditions.
