Muscarinic antagonist
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Needs more citations. Includes a large table which needs to be turned into prose or removed. | |
Class identifiers | |
---|---|
Use | Allergies, asthma, atrial fibrillation with bradycardia,[1] motion sickness, Parkinson's disease, etc. |
ATC code | V |
Biological target | Metabotropic acetylcholinergic receptors |
External links | |
MeSH | D018727 |
Legal status | |
In Wikidata |
A muscarinic receptor antagonist (MRA), also called an antimuscarinic, is a type of anticholinergic agent that blocks the activity of the muscarinic acetylcholine receptor. The muscarinic receptor is a protein involved in the transmission of signals through certain parts of the nervous system, and muscarinic receptor antagonists work to prevent this transmission from occurring. Notably, muscarinic antagonists reduce the activation of the parasympathetic nervous system. The normal function of the parasympathetic system is often summarised as "rest-and-digest", and includes slowing of the heart, an increased rate of digestion, narrowing of the airways, promotion of urination, and sexual arousal. Muscarinic antagonists counter this parasympathetic "rest-and-digest" response, and also work elsewhere in both the central and peripheral nervous systems.
Drugs with muscarinic antagonist activity are widely used in medicine, in the treatment of low heart rate, overactive bladder, respiratory problems such as asthma and COPD, and neurological problems such as Parkinson's disease and Alzheimer's disease. A number of other drugs, such as antipsychotics and the tricyclic family of antidepressants, have incidental muscarinic antagonist activity which can cause unwanted side effects such as difficulty urinating, dry mouth and skin, and constipation.
Acetylcholine (often abbreviated ACh) is a neurotransmitter whose receptors are proteins found in synapses and other cell membranes. Besides responding to their primary neurochemical, neurotransmitter receptors can be sensitive to a variety of other molecules. Acetylcholine receptors are classified into two groups based on this:
Most muscarinic receptor antagonists are synthetic chemicals; however, the two most commonly used anticholinergics,
Muscarinic antagonist effects and muscarinic agonist effects counterbalance each other for homeostasis.
Certain muscarinic antagonists can be classified into either long-acting muscarinic receptor antagonists (LAMAs) or short-acting muscarinic receptor antagonists (SAMAs), depending on when maximum effect occurs and for how long the effect persists.[3]
Effects
This section needs additional citations for verification. (March 2024) |
Antimuscarinics are also used as anti-parkinsonian drugs. In parkinsonism, there is imbalance between levels of acetylcholine and dopamine in the brain, involving both increased levels of acetylcholine and degeneration of dopaminergic pathways (nigrostriatal pathway). Thus, in parkinsonism there is decreased level of dopaminergic activity. One method of balancing the neurotransmitters is through blocking central cholinergic activity using muscarinic receptor antagonists.
Atropine acts on the
In the
Important
Muscarinic antagonists such as
Comparison table
This section is in prose. is available. (March 2024) |
Overview
Substance | Selectivity | Clinical use | Adverse effects | Notes | Trade names |
---|---|---|---|---|---|
Atropine (D/L-Hyoscyamine) | NS |
|
CD[5] | Symax, HyoMax, Anaspaz, Egazil, Buwecon, Cystospaz, Levsin, Levbid, Levsinex, Donnamar, NuLev, Spacol T/S and Neoquess | |
Atropine methonitrate
|
NS |
|
Blocks transmission in | ||
Aclidinium bromide | Selective[clarification needed] |
|
Long acting antagonist | Tudorza | |
Benztropine | M1 -selective
|
|
Reduces the effects of the relative central cholinergic excess that occurs as a result of dopamine deficiency. | Cogentin | |
Cyclopentolate | NS |
|
|
Short acting, CD[5] | |
Diphenhydramine | NS |
|
|
Acts in the central nervous system, blood vessels and smooth muscle tissues | Nytol
|
Doxylamine | NS |
|
|
Unisom | |
Dimenhydrinate | Combination of diphenhydramine with a methylxanthine salt | Dramamine, Gravol | |||
Dicyclomine
|
Bentyl | ||||
Darifenacin | Selective for M3[7]
|
Urinary incontinence [7] | Few side effects[7] | Enablex | |
Flavoxate |
|
Urispas | |||
Glycopyrrolate (Glycopyrronium bromide) | NS |
|
Does not cross the blood–brain barrier and has few to no central effects.[9] | Robinul, Cuvposa, Seebri | |
Hydroxyzine | Very mild/negligible action | Vistaril, Atarax | |||
Ipratropium bromide
|
NS | Asthma and bronchitis[5] |
|
Lacks mucociliary excretion inhibition.[5]
|
Atrovent and Apovent |
Mebeverine |
|
|
A muscolotropic spasmolytic with a strong and selective action on the smooth muscle spasm of the gastrointestinal tract, in particular of the colon. | Colofac, Duspatal, Duspatalin | |
Oxybutynin | M1/3/4 selective |
|
Ditropan | ||
Pirenzepine | M1-selective[5]
|
|
(fewer than non-selective ones)[5] | Inhibits gastric secretion[5]
|
|
Procyclidine | NS |
|
Overdose produces confusion, agitation and sleeplessness that can last up to or more than 24 hours. Pupils become dilated and unreactive to light. Tachycardia (fast heart beat), as well as auditory and visual hallucinations | ||
Scopolamine (L-Hyoscine)
|
NS |
|
CD[5] | Scopace, Transderm-Scop, Maldemar, Buscopan | |
Solifenacin |
|
Competitive antagonist | Vesicare | ||
Tropicamide | NS |
|
|
Short acting, CD[5] | |
Tiotropium
|
Spiriva | ||||
Benzhexol
|
M1 selective | PD | Drug at relative dose has 83% activity of atropine, thus has the same side-effects | Artane | |
Tolterodine |
|
Detrusitol, Detrol |
Binding affinities
Anticholinergics
Compound | M1 | M2 | M3 | M4 | M5 | Species | Ref |
---|---|---|---|---|---|---|---|
3-Quinuclidinyl benzilate | 0.035–0.044 | 0.027–0.030 | 0.080–0.088 | 0.034–0.037 | 0.043–0.065 | Human | [10][11] |
4-DAMP | 0.57–0.58 | 3.80–7.3 | 0.37–0.52 | 0.72–1.17 | 0.55–1.05 | Human | [12][13] |
AF-DX 250 | 427 | 55.0 | 692 | 162 | 3020 | Human | [12] |
AF-DX 384 | 30.9 | 6.03 | 66.1 | 10.0 | 537 | Human | [12] |
AQ-RA 741 | 28.8 | 4.27 | 63.1 | 6.46 | 832 | Human | [12] |
Atropine | 0.21–0.50 | 0.76–1.5 | 0.15–1.1 | 0.13–0.6 | 0.21–1.7 | Human | [10][14][13] |
Benzatropine (benztropine) | 0.231 | 1.4 | 1.1 | 1.1 | 2.8 | Human | [10] |
Biperiden | 0.48 | 6.3 | 3.9 | 2.4 | 6.3 | Human | [10] |
Darifenacin | 5.5–13 | 47–77 | 0.84–2.0 | 8.6–22 | 2.3–5.4 | Human | [13][15] |
Dicycloverine (dicyclomine) | 57 (IC50) | 415 (IC50) | 67 (IC50) | 97 (IC50) | 53 (IC50) | Human/rat | [14] |
Glycopyrrolate |
0.37 | 1.38 | 1.31 | 0.41 | 1.30 | Human | [9] |
Hexahydrodifenidol | 11 | 200 | 16 | 76 (IC50) | 83 | Human/rat | [14] |
Hexahydrosiladifenidol | 44 | 249 | 10 | 298 (IC50) | 63 | Human/rat | [14] |
(R)-Hexbutinol | 2.09 | 20.9 | 2.14 | 3.02 | 5.50 | Human | [12] |
Hexocyclium | 2.3 | 23 | 1.4 | 5.5 | 3.7 | Human/rat | [14] |
Himbacine | 107 | 10.0 | 93.3 | 11.0 | 490 | Human | [12] |
Ipratropium |
0.49 | 1.5 | 0.51 | 0.66 | 1.7 | Human | [15] |
Methoctramine | 16–50 | 3.6–14.4 | 118–277 | 31.6–38.0 | 57–313 | Human | [14][12][16] |
N-Methylscopolamine |
0.054–0.079 | 0.083–0.251 | 0.052–0.099 | 0.026–0.097 | 0.106–0.125 | Human | [12] |
Orphenadrine | 48 | 213 | 120 | 170 | 129 | Human | [11] |
Otenzepad (AF-DX 116) | 1300 | 186 | 838 | 1800 (IC50) | 2800 | Human/rat | [14] |
Oxybutynin | 0.66 | 13 | 0.72 | 0.54 | 7.4 | Human | [13] |
pFHHSiD | 22.4 | 132 | 15.5 | 31.6 | 93.3 | Human | [12] |
Pirenzepine | 6.3–8 | 224–906 | 75–180 | 17–37 | 66–170 | Human | [10][14][12][13] |
Procyclidine | 4.6 | 25 | 12.4 | 7 | 24 | Human | [10] |
Propiverine | 476 | 2970 | 420 | 536 | 109 | Human | [13] |
Scopolamine (hyoscine) | 1.1 | 2.0 | 0.44 | 0.8 | 2.07 | Human | [10] |
Silahexacyclium | 2.0 | 35 | 1.2 | 3.2 | 2.0 | Human/rat | [14] |
Timepidium |
34 | 7.7 | 31 | 18 | 11 | Human | [13] |
Tiquizium | 4.1 | 4.0 | 2.8 | 3.6 | 8.2 | Human | [13] |
Trihexyphenidyl | 1.6 | 7 | 6.4 | 2.6 | 15.9 | Human | [10] |
Tripitamine (tripitramine) | 1.58 | 0.27 | 38.25 | 6.41 | 33.87 | Human | [16] |
Zamifenacin | 55 | 153 | 10 | 68 | 34 | Human | [13] |
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site. |
Antihistamines
Compound | M1 | M2 | M3 | M4 | M5 | Species | Ref |
---|---|---|---|---|---|---|---|
Brompheniramine | 25700 | 32400 | 50100 | 67600 | 28800 | Human | [17] |
Chlorphenamine (chlorpheniramine) | 19000 | 17000 | 52500 | 77600 | 28200 | Human | [17] |
Cyproheptadine | 12 | 7 | 12 | 8 | 11.8 | Human | [11] |
Diphenhydramine | 80–100 | 120–490 | 84–229 | 53–112 | 30–260 | Human | [10][18] |
Doxylamine | 490 | 2100 | 650 | 380 | 180 | Human | [18] |
Mequitazine | 5.6 | 14 | 5.3 | 11.1 | 11.0 | Human | [11] |
Terfenadine | 8710 | 8510 | 5250 | 30900 | 11200 | Human | [17] |
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site. |
Antidepressants
Compound | M1 | M2 | M3 | M4 | M5 | Species | Ref |
---|---|---|---|---|---|---|---|
Amitriptyline | 14.7 | 11.8 | 12.8 | 7.2 | 15.7 | Human | [11] |
Bupropion | >35,000 | >35,000 | >35,000 | >35,000 | >35,000 | Human | [11] |
Citalopram | 1430 | ND | ND | ND | ND | Human | [19] |
Desipramine | 110 | 540 | 210 | 160 | 143 | Human | [11] |
Desmethylcitalopram | >10000 | >10000 | >10000 | >10000 | >10000 | Human | [20] |
Desmethyldesipramine | 404 | 927 | 317 | 629 | 121 | Human | [20] |
Desvenlafaxine | >10000 | >10000 | >10000 | >10000 | >10000 | Human | [21] |
Dosulepin (dothiepin) | 18 | 109 | 38 | 61 | 92 | Human | [11] |
Doxepin | 18–38 | 160–230 | 25–52 | 20–82 | 5.6–75 | Human | [18][11] |
Escitalopram | 1242 | ND | ND | ND | ND | Human | [19] |
Etoperidone | >35000 | >35000 | >35000 | >35000 | >35000 | Human | [11] |
Femoxetine | 92 | 150 | 220 | 470 | 400 | Human | [11] |
Fluoxetine | 702–1030 | 2700 | 1000 | 2900 | 2700 | Human | [11][19] |
Fluvoxamine | 31200 | ND | ND | ND | ND | Human | [19] |
Imipramine | 42 | 88 | 60 | 112 | 83 | Human | [11] |
Lofepramine | 67 | 330 | 130 | 340 | 460 | Human | [11] |
Norfluoxetine |
1200 | 4600 | 760 | 2600 | 2200 | Human | [11] |
Nortriptyline | 40 | 110 | 50 | 84 | 97 | Human | [11] |
Paroxetine | 72–300 | 340 | 80 | 320 | 650 | Human | [11][19] |
Sertraline | 427–1300 | 2100 | 1300 | 1400 | 1900 | Human | [11][19] |
Tianeptine | >10000 | >10000 | >10000 | >10000 | >10000 | Human | [22] |
Trazodone | >35,000 | >35,000 | >35,000 | >35,000 | >35,000 | Human | [18][11] |
Venlafaxine | >35000 | >35000 | >35000 | >35000 | >35000 | Human | [11] |
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site. |
Antipsychotics
Compound | M1 | M2 | M3 | M4 | M5 | Species | Ref |
---|---|---|---|---|---|---|---|
Amisulpride | >10,000 | >10,000 | >10,000 | >10,000 | >10,000 | Human | [23] |
Aripiprazole | 6780 | 3510 | 4680 | 1520 | 2330 | Human | [24] |
Asenapine | >10000 | >10000 | >10000 | >10000 | ND | Human | [25] |
Bromperidol | 7600 | 1800 | 7140 | 1700 | 4800 | Human | [10] |
Chlorprothixene | 11 | 28 | 22 | 18 | 25 | Human | [10] |
Chlorpromazine | 25 | 150 | 67 | 40 | 42 | Human | [10] |
Clozapine | 1.4–31 | 7–204 | 6–109 | 5–27 | 5–26 | Human | [10][25][26][27] |
Cyamemazine (cyamepromazine) | 13 | 42 | 32 | 12 | 35 | Human | [28] |
N-Desmethylclozapine | 67.6 | 414.5 | 95.7 | 169.9 | 35.4 | Human | [29] |
Fluperlapine | 8.8 | 71 | 41 | 14 | 17 | Human | [10] |
Fluphenazine | 1095 | 7163 | 1441 | 5321 | 357 | Human | [30] |
Haloperidol | >10000 | >10000 | >10000 | >10000 | >10000 | Human | [25][26] |
Iloperidone | 4898 | 3311 | >10000 | 8318 | >10000 | Human | [31] |
Loxapine | 63.9–175 | 300–590 | 122–390 | 300–2232 | 91–241 | Human | [10][32] |
Melperone | >15000 | 2400 | >15000 | 4400 | >15000 | Human | [10] |
Mesoridazine | 10 | 15 | 90 | 19 | 60 | Human | [10] |
Molindone | ND | ND | >10000 | ND | ND | Human | [33] |
Olanzapine | 1.9–73 | 18–96 | 13–132 | 10–32 | 6–48 | Human | [25][26][27] |
Perphenazine | ND | ND | 1848 | ND | ND | Human | [33] |
Pimozide | ND | ND | 1955 | ND | ND | Human | [33] |
Quetiapine | 120–135 | 630–705 | 225–1320 | 660–2990 | 2990 | Human | [25][26] |
Remoxipride | >10000 | >10000 | >10000 | >10000 | ND | Human | [25] |
Rilapine | 190 | 470 | 1400 | 1000 | 1100 | Human | [10] |
Risperidone | 11000 | ≥3700 | 13000 | ≥2900 | >15000 | Human | [10][25] |
Sertindole | ND | ND | 2692 | ND | ND | Human | [33] |
Tenilapine | 260 | 62 | 530 | 430 | 660 | Human | [10] |
Thioridazine | 2.7 | 14 | 15 | 9 | 13 | Human | [10] |
Thiothixene |
>10000 | >10000 | >10000 | >10000 | 5376 | Human | [34] |
cis-Thiothixene |
2600 | 2100 | 1600 | 1540 | 4310 | Human | [10] |
Tiospirone | 630 | 180 | 1290 | 480 | 3900 | Human | [10] |
Trifluoperazine | ND | ND | 1001 | ND | ND | Human | [33] |
Ziprasidone | ≥300 | >3000 | >1300 | >1600 | >1600 | Human | [26][35] |
Zotepine | 18 | 140 | 73 | 77 | 260 | Human | [10] |
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site. |
See also
References
- ^ a b "Hyoscyamine Subs for Pacemaker in Afib with Bradycardia". www.medpagetoday.com. May 14, 2018.
- ^ "Belladonna: MedlinePlus Supplements". medlineplus.gov. Retrieved 2020-08-13.
- OCLC 1081403059.)
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- ^ Roth, BL; Driscol, J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
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- ^ Roth, BL; Driscol, J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
- ^ Roth, BL; Driscol, J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
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- ^ Roth, BL; Driscol, J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
- ^ PMID 12629531.
- ^ Roth, BL; Driscol, J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
- ^ Roth, BL; Driscol, J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
External links
- Effects of Muscarinic Antagonist
- Atropine (Muscarinic Receptor Antagonist), Cardiovascular Pharmacology Concepts, Richard E. Klabunde, PhD
- Muscarinic+antagonists at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- MeSH list of agents 82018727