Rizatriptan

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Rizatriptan, sold under the brand name Maxalt among others, is a medication used for the treatment of migraine headaches.[1][2] It is taken by mouth.[1][2] It can also be applied on the tongue.[3] It is a serotonin (5-HT) 1B/1D receptor agonist (triptan).[1][3]

Common side effects include chest pain, dizziness, dry mouth, and tingling.[2] Other side effects may include myocardial infarction, stroke, high blood pressure, serotonin syndrome, and anaphylaxis.[2] Excessive use may result in medication overuse headaches.[2] Use is not recommended during pregnancy and breastfeeding is not recommended within 24 hours after taking a dose.[4] Rizatriptan is in the triptan class and is believed to work by activating the 5-HT1 receptor.[2]

Rizatriptan was patented in 1991 and came into medical use in 1998.[5][6] It is available as a generic medication.[4] In 2023, it was the 208th most commonly prescribed medication in the United States, with more than 2Script error: No such module "String".million prescriptions.[7][8] Rizatriptan is available in combination with meloxicam as meloxicam/rizatriptan.

Medical uses

Rizatriptan is indicated to treat acute migraine attacks with or without aura.[1][3] It does not prevent future migraine attacks.[9] A 2010 review found rizatriptan to be more efficacious and tolerable than sumatriptan.[10]

Contraindications

Rizatriptan and other triptans can cause vasoconstriction, they are contraindicated in people with cardiovascular conditions.[11]

Adverse effects

Frequent adverse effects (incidence less than 10%) are dizziness, drowsiness, asthenia/fatigue, and nausea. Clinical adverse experiences were typically mild and short-lasting (2–3 hours).[11]

Interactions

Rizatriptan has an important but complex interaction with a metabolite of the beta blocker propranolol.[12] This interaction involves the enzyme monoamine oxidase A (MAO-A).[12] Due to the interaction, the dose of rizatriptan should be reduced to 5Script error: No such module "String".mg when it is combined with propranolol.[12]

Pharmacology

Mechanism of action

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Rizatriptan activities
Target Affinity (Ki, nM)
5-HT1A 48–500 (Ki)
>10,000 (EC50Tooltip half-maximal effective concentration)
40% (EmaxTooltip maximal efficacy)
5-HT1B 3–138 (Ki)
1.4–234 (EC50)
74–99% (Emax)
5-HT1D 1.5–138 (Ki)
1.6–16 (EC50)
83–105% (Emax)
5-HT1E 87–316 (Ki)
6.8–870 (EC50)
107% (Emax)
5-HT1F 138–5,370 (Ki)
4.2–2,540 (EC50)
93% (Emax)
5-HT2A >10,000 (Ki)
>10,000 (EC50)
5-HT2B 257–3,090 (Ki)
3,240 (EC50)
5-HT2C >3,160 (Ki)
ND (EC50)
5-HT3 >3,160 (mouse)
5-HT4 >3,160 (guinea pig)
5-HT5A 5,500 (rat)
5-HT6 >3,160
5-HT7 1,860–>10,000 (Ki)
>10,000 (EC50)
α1Aα1D ND
α2Aα2C ND
β1β3 ND
D1D5 ND
H1H4 ND
M1M5 ND
I1, I2 ND
σ1, σ2 ND
TAAR1Tooltip Trace amine-associated receptor 1 ND
SERTTooltip Serotonin transporter ND
NETTooltip Norepinephrine transporter ND
DATTooltip Dopamine transporter ND
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [13][14][15][16][17][18][19]
[20][21][22][23][24][25][26]

Rizatriptan acts as an agonist at serotonin 5-HT1B and 5-HT1D receptors.[27] Like the other triptans sumatriptan and zolmitriptan, rizatriptan induces vasoconstriction—possibly by inhibiting the release of calcitonin gene-related peptide from sensory neurons in the trigeminal nerve.[27]

Chemistry

Rizatriptan, also known as 5-(1H-1,2,4-triazol-1-ylmethyl)-N,N-dimethyltryptamine, is a tryptamine derivative and a 5-substituted derivative of the psychedelic drug dimethyltryptamine (DMT).[28]

The experimental log P of rizatriptan is 1.4 and its predicted log P is 1.67 to 1.77.[28][29]

History

Rizatriptan was patented in 1991 and was introduced for medical use in 1998.[5][6]

Society and culture

Brand names

Brand names include Rizalt, Rizalt RPD, Rizact (India), Rizafilm,[3] Maxalt,[1] and Maxalt-MLT.[1][30][31][32]

References

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