MECHANISM OF ACTION –
Pregabalin binds with high affinity to the alpha2-delta site (an auxiliary subunit of voltage-gated calcium channels) in central nervous system tissues. Although the mechanism of action of pregabalin is unknown, results with genetically modified mice and with compounds structurally related to pregabalin (such as gabapentin) suggest that binding to the alpha2-delta subunit may be involved in pregabalin's antinociceptive and antiseizure effects in animal models. In vitro, pregabalin reduces the calcium-dependent release of several neurotransmitters, possibly by modulation of calcium channel function. Studies also suggest that the descending noradrenergic and serotonergic pathways originating from the brainstem may be involved with the mechanism of pregabalin. Interestingly, although pregabalin is a structural derivative of inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABA or benzodiazepine receptors. The sodium channels, opiate receptors, and cyclooxygenase enzymes are not involved with the mechanism of pregabalin. It is also inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.
PHARMACOLOGICAL ACTION –
1-Pregabalin binds to the alpha2-delta subunit of the voltage-gated calcium channel in the central nervous system.
2- While pregabalin is a structural derivative of the inhibitory neurotransmitter gamma- aminobutyric acid (GABA), it does not bind directly to GABA-A, GABA-B, or benzodiazepine receptors, does not augment GABA-A responses in cultured neurons, does not alter rat brain GABA concentration or have acute effects on GABA uptake or degradation.
3-However, in cultured neurons prolonged application of pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport.
4-Pregabalin does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity.
5- It is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.
USES –
1. It is used to treat pain caused by nerve damage due to diabetes or to shingles (herpes zoster) infection.
2. It may also be used to treat nerve pain caused by spinal cord injury.
3. This is also used to treat pain in people with fibromyalgia.
4. It is also used with other medications to treat certain types of seizures.
SIDE EFFECTS –
1-Drowsiness
2-Dizziness
3-Dry mouth
4-Constipation
5-Swollen arms
6-Weight gain.
DRUG-DRUG INTERACTION –
1-Pregabalin + Azelastine = may increase the CNS depressant activity of Azelastine.
2-Pregabalin + Captopril = risk or severity of adverse effect can be increase.
3-Pregabalin + Benazapril = risk or severity of adverse effect can be increase.
REFERENCE-
Tripathi K.D,"Essentials of medical pharmacology",7th edition,page no.419
Pregabalin binds with high affinity to the alpha2-delta site (an auxiliary subunit of voltage-gated calcium channels) in central nervous system tissues. Although the mechanism of action of pregabalin is unknown, results with genetically modified mice and with compounds structurally related to pregabalin (such as gabapentin) suggest that binding to the alpha2-delta subunit may be involved in pregabalin's antinociceptive and antiseizure effects in animal models. In vitro, pregabalin reduces the calcium-dependent release of several neurotransmitters, possibly by modulation of calcium channel function. Studies also suggest that the descending noradrenergic and serotonergic pathways originating from the brainstem may be involved with the mechanism of pregabalin. Interestingly, although pregabalin is a structural derivative of inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABA or benzodiazepine receptors. The sodium channels, opiate receptors, and cyclooxygenase enzymes are not involved with the mechanism of pregabalin. It is also inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.
PHARMACOLOGICAL ACTION –
1-Pregabalin binds to the alpha2-delta subunit of the voltage-gated calcium channel in the central nervous system.
2- While pregabalin is a structural derivative of the inhibitory neurotransmitter gamma- aminobutyric acid (GABA), it does not bind directly to GABA-A, GABA-B, or benzodiazepine receptors, does not augment GABA-A responses in cultured neurons, does not alter rat brain GABA concentration or have acute effects on GABA uptake or degradation.
3-However, in cultured neurons prolonged application of pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport.
4-Pregabalin does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity.
5- It is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.
USES –
1. It is used to treat pain caused by nerve damage due to diabetes or to shingles (herpes zoster) infection.
2. It may also be used to treat nerve pain caused by spinal cord injury.
3. This is also used to treat pain in people with fibromyalgia.
4. It is also used with other medications to treat certain types of seizures.
SIDE EFFECTS –
1-Drowsiness
2-Dizziness
3-Dry mouth
4-Constipation
5-Swollen arms
6-Weight gain.
DRUG-DRUG INTERACTION –
1-Pregabalin + Azelastine = may increase the CNS depressant activity of Azelastine.
2-Pregabalin + Captopril = risk or severity of adverse effect can be increase.
3-Pregabalin + Benazapril = risk or severity of adverse effect can be increase.
REFERENCE-
Tripathi K.D,"Essentials of medical pharmacology",7th edition,page no.419
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