mAChR

In coronary artery smooth muscle cells, oxybutynin (0.1, 0.3, 1, 3, 10, 30, 100 μM; 200 ms) inhibits vascular Kv channels in a concentration-dependent manner without affecting the anticholinergic effect[1].

When specific [3H]N-methylscopolamine binding occurs 0.5 and 2 hours later, oxybutynin (27.2 mg/kg; po; single) significantly binds mouse brain muscarinic receptors, increasing Kd values by about a factor of two[2].

This study demonstrates the inhibitory effect of anticholinergic drug oxybutynin on voltage-dependent K+ (Kv) channels in rabbit coronary arterial smooth muscle cells. Oxybutynin inhibited vascular Kv channels in a concentration-dependent manner, with an IC50 value of 11.51 ± 0.38 μmol/L and a Hill coefficient (n) of 2.25 ± 0.12. Application of oxybutynin shifted the activation curve to the right and the inactivation curve to the left. Pretreatment with the Kv1.5 subtype inhibitor DPO-1 and the Kv2.1 subtype inhibitor guangxitoxin suppressed the oxybutynin-induced inhibition of the Kv current. However, application of the Kv7 subtype inhibitor linopirdine did not affect the inhibition by oxybutynin of the Kv current. The anticholinergic drug atropine did not inhibit the Kv current nor influence oxybutynin-induced inhibition of the Kv current. From these results, we concluded that oxybutynin inhibited the vascular Kv current in a concentration-dependent manner by influencing the steady-state activation and inactivation curves independent of its anticholinergic effect[1].

Cell Viability Assay[1]
Cell Types: Coronary arterial smooth muscle cells (from male New Zealand White rabbits)
Tested Concentrations: 10 μM
Incubation Duration: 200 ms
Experimental Results: Rapidly inhibited the Kv current within 2 min and decreased the Kv current by 44% at +60 Mv. Inhibited the Kv current by changing the gating properties of Kv channels.

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Cell Viability Assay[1]
Cell Types: Coronary arterial smooth muscle cells (from male New Zealand White rabbits)
Tested Concentrations: 0.1, 0.3, 1, 3, 10, 30, 100 μM
Incubation Duration: 200 ms
Experimental Results: decreased the Kv current amplitude in a concentration-dependent manner, with an IC50 value of 11.51 μM.

Animal/Disease Models: Male ddY strain mice (9 to 13weeks old)[2].
Doses: 27.2 mg/kg (76.1 µmol/kg)
Route of Administration: Oral administration; single.
Experimental Results: Significant increased Kd values for specific [3H]NMS binding in Significant increased Kd values for specific [3H]NMS binding in mouse cerebral cortex with values of 120% and 71.2% when at 0.5 and 2 hrs (hours), respectively. .

Absorption, Distribution and Excretion
Oxybutynin should be swallowed whole with the help of liquids. A pharmacokinetic study revealed that oxybutynin was rapidly absorbed, and peak concentrations were reached within about 1 hour of administration, measured at 8.2 ngml-1 and AUC was 16 ngml-1. The biovailability of oxybutynin is about 6%, and the plasma concentration of the active metabolite, desethyloxybutynin is 5 to 12 times greater than that of oxybutynin. Bioavailability is increased in the elderly. Food has been shown to increase the exposure to controlled-release oxybutynin.
Oxybutynin is heavily cleared by the liver. Under 0.1% of an administered dose is found as unchanged drug in the urine. Less than 0.1% of a single dose of oxybutynin is excreted as desethyloxybutynin.
Oxybutynin has a wide volume of distribution of 193 L. In rats, oxybutynin penetrates the central nervous system.

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Metabolism / Metabolites
Oxybutynin is heavily metabolized by the CYP3A4 enzyme system in both the liver and the wall of the intestine. It undergoes first-pass metabolism, and its resulting primary active metabolite, N-desethyloxybutynin circulates. It is active at the muscarinic receptors in both the bladder and the salivary gland. Hepatic biotransformation also produces its major inactive metabolite, phenylcyclohexylglycolic acid.

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Biological Half-Life
The plasma elimination half-life is about 2 hours. In the elderly, the elimination half-life is prolonged up to 5 hours.

Hepatotoxicity
In multiple, large clinical trials of oxybutynin therapy for overactive bladder syndrome, serum enzyme elevations were rare and no more frequent than with placebo, and there were no episodes of clinically apparent liver injury. Since its approval and widespread use for more than four decades, there has been only a single published case of suspected liver injury attributed to oxybutynin – a report of transient serum enzyme elevations without jaundice or apparent symptoms in a patient with a severe ischemic stroke arising within weeks of starting oxybutynin. Thus, clinically apparent liver injury from oxybutynin is very rare if it occurs at all.
Likelihood score: E (unlikely cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the use of oxybutynin during breastfeeding. Long-term use of oxybutynin might reduce milk production or milk letdown, but a single dose is not likely to interfere with breastfeeding. During long-term use, observe for signs of decreased lactation (e.g., insatiety, poor weight gain).
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Anticholinergics can inhibit lactation in animals, apparently by inhibiting growth hormone and oxytocin secretion. Anticholinergic drugs can also reduce serum prolactin in nonnursing women. The prolactin level in a mother with established lactation may not affect her ability to breastfeed. The manufacturer reports that cases of lactation suppression have been reported with some oxybutynin (immediate-release) formulations in postmarketing surveillance.

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Protein Binding
Oxybutynin enantiomers are more than 97% bound to plasma proteins, primarily to alpha-1 acid glycoprotein.

[1]. The anticholinergic drug oxybutynin inhibits voltage-dependent K+ channels in coronary arterial smooth muscle cells. Clin Exp Pharmacol Physiol. 2019 Nov;46(11):1030-1036.

[2]. Comparative evaluation of central muscarinic receptor binding activity by oxybutynin, tolterodine and darifenacin used to treat overactive bladder. J Urol. 2007 Feb;177(2):766-70.

Oxybutynin is a racemate comprising equimolar amounts of (R)-oxybutynin and esoxybutynin. An antispasmodic used for the treatment of overactive bladder. It has a role as a muscarinic antagonist, a muscle relaxant, an antispasmodic drug, a parasympatholytic, a calcium channel blocker and a local anaesthetic. It is a tertiary amino compound and a racemate. It contains an esoxybutynin and a (R)-oxybutynin.
Overactive bladder (OAB) is a common condition negatively impacting the lives of millions of patients worldwide. Due to its urinary symptoms that include nocturia, urgency, and frequency, this condition causes social embarrassment and a poor quality of life. Oxybutynin, also marketed as Ditropan XL, is an anticholinergic medication used for the relief of overactive bladder symptoms that has been optimized for high levels of safety and efficacy since initial FDA approval in 1975. This drug relieves undesirable urinary symptoms, increasing the quality of life for patients affected by OAB. It is often used as first-line therapy for OAB.
Oxybutynin is a Cholinergic Muscarinic Antagonist. The mechanism of action of oxybutynin is as a Cholinergic Muscarinic Antagonist.
Oxybutynin is a synthetic anticholinergic agent that is used for treatment of urinary incontinence and overactive bladder syndrome. Oxybutynin has not been implicated in causing liver enzyme elevations or clinically apparent acute liver injury.
Oxybutynin is a tertiary amine possessing antimuscarinic and antispasmodic properties. Oxybutynin blocks muscarinic receptors in smooth muscle, hence inhibiting acetylcholine binding and subsequent reduction of involuntary muscle contractions. Oxybutynin is used to reduce bladder contractions by relaxing bladder smooth muscle.
See also: Oxybutynin Chloride (has salt form).

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Drug Indication
Oxybutynin is indicated for the symptomatic treatment of overactive bladder, which causes urge urinary incontinence and frequency, and urgency. Oxybutynin may also be used for children aged 6 and above for the symptomatic management of detrusor muscle overactivity which has been found to be related to a neurological condition. Spina bifida is an example of a neurological condition in which oxybutynin may be used to control urinary symptoms. On occasion, oxybutynin may be used off-label to relieve bladder spasms associated with ureteral stents or urinary catheters.
Symptomatic treatment of urge incontinence and/or increased urinary frequency and urgency as may occur in adult patients with unstable bladder.

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Mechanism of Action
Oxybutynin acts to relax the bladder by inhibiting the muscarinic action of acetylcholine on smooth muscle, and not skeletal muscle. The active of oxybutynin is metabolite is N-desethyloxybutynin. It competitively inhibits the postganglionic type 1, 2 and 3 muscarinic receptors. The above actions lead to increased urine capacity in the bladder, decreasing urinary urgency and frequency. In addition, oxybutynin delays the initial desire to void.
RESULTS OF CYSTOMETRIC STUDIES SHOWED THAT THE DRUG INCR BLADDER CAPACITY @ ONSET OF FIRST CONTRACTION & FIRST DESIRE TO VOID, AS WELL AS @ END OF CYSTOMETRY. /CHLORIDE/

C22H31NO3

357.49

357.23

C, 73.92; H, 8.74; N, 3.92; O, 13.43

5633-20-5

Oxybutynin;5633-20-5;Oxybutynin chloride;1508-65-2;(R)-Oxybutynin hydrochloride;1207344-05-5;Oxybutynin-d11 chloride;1185151-95-4; Oxybutynin;5633-20-5;(R)-Oxybutynin hydrochloride;1207344-05-5;Oxybutynin-d11 chloride;1185151-95-4;(R)-Oxybutynin;119618-21-2; 5633-20-5 (racemate); 1508-65-2 (racemate HCl); 1207344-05-5 (R-isomer HCl); 119618-21-2 (R-isomer); 2738613-22-2 (R-isomer citrate); 119618-22-3 (S-isomer); 2862851-81-6 (R-isomer tartrate); 230949-16-3 (S-isomer HCl)

4634

Typically exists as White to off-white solids at room temperature

1.1±0.1 g/cm3

494.4±45.0 °C at 760 mmHg

125 - 130ºC

252.8±28.7 °C

0.0±1.3 mmHg at 25°C

1.546

5.19

1

4

8

26

490

0

O([H])C(C(=O)OC([H])([H])C#CC([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])[H])(C1C([H])=C([H])C([H])=C([H])C=1[H])C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H]

XIQVNETUBQGFHX-UHFFFAOYSA-N

InChI=1S/C22H31NO3/c1-3-23(4-2)17-11-12-18-26-21(24)22(25,19-13-7-5-8-14-19)20-15-9-6-10-16-20/h5,7-8,13-14,20,25H,3-4,6,9-10,15-18H2,1-2H3

4-(diethylamino)but-2-ynyl 2-cyclohexyl-2-hydroxy-2-phenylacetate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: 2.08 mg/mL (5.82 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (5.82 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (5.82 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)