• Duboisia
    Duboisia
  • Duboisia
    Duboisia

Butylscopolamine

HYOSCINE-BUTYLBROMIDE (EP)

EP
DMF

One of the earliest alkaloids to be isolated from plant sources is Scopolamine, which has been in use since it was isolated by the German scientist Albert Ladenburg in 1880. The use of various preparations from its plant-based form is learnt from the healing arts of some of the world’s oldest cultures and perhaps even pre-historic times.

In India Ancient Hindu physicians knew of the antispasmodic effects of a relative of the Duboisia shrub. In the search for a safe and effective treatment for abdominal pain and cramp, scientists based at Ingelheim prepared a semisynthetic derivative from the extract of elite Duboisia plants grown in greenhouses. This molecule, Butylscopolamine, was free of the undesirable side-effects on the central nervous system, typical of Scopolamine, and the medication, on sale since 1952, was immediately recognized as a safe and effective antispasmodic.

Today, Butylscopolamine, also known as Scopolamine butylbromide, butylhyoscine or hyoscine butylbromide, is the world’s leading and most trusted treatment for pain and discomfort caused by muscle spasms and cramps. It cannot be considered an analgesic in the normal sense, in that it does not ‘mask’ or ‘cover’ the pain, but rather works to prevent the pain from occurring in the first place.

Source

Linnea Butylscopolamine is derived from the leaves of an Australian native tree, known as the corkwood tree or Duboisia myoporoides belonging to the Solanaceae family.

Scopolamine butylbromide is obtained from Scopolamine isolated and purified from dried Duboisia leaves and stalks harvested on specialized plantations. These plantations had initially been established by the government of Queensland for the extraction of Scopolamine for use as a surgical anaesthetic during the Second World War [1]. In the mid-1950s, the plantations were purchased and managed by Australian farmers (A), who now use sophisticated and environmentally-friendly farming methods that respect the rules of GAP (Good Agricultural Practice) and ensure full process traceability.

Activity

Butylscopolamine, like its precursor Scopolamine, has a high affinity for acetylcholine receptors located on smooth-muscle cells. It blocks the action Butylscopolamine decreases the motility of the gastrointestinal tract and the genitourinary tract and is useful in the treatment of spasms in these regions, as may be seen in gastroenteritis, colitis, inflammatory bowel disease, diverticulitis, biliary colic, cystitis, ureteric colic and primary dysmenorrhea. The inhibitory action on glands in the oral cavity, gastrointestinal tract, and respiratory tract causes a reduction in secretion.

The scientific base of its activity was objectively demonstrated by a recent study conducted to investigate its electrical and biomechanical activity in the stomach. A quantity of 20 mg of intravenous Butylscopolamine was shown to decrease both the mechanical and electrical motility index [3,4]. The addition of the butyl-bromide moiety to Scopolamine has resulted in a significant increase in the water solubility of this drug, which effectively prevents movement across the blood-brain barrier with a marked peripheral activity.

Since it is only partially absorbed following oral administration, it remains available at the site of action in the intestine and has a local relaxing/spasmolytic effect with a low systemic availability.

Common Applications and Evidence

Common applications

Scopolamine butylbromide is a generally safe and affordable drug with a wide range of applications. It was originally used as a treatment for non-specific colicky abdominal pain (in adults and children) for which it is currently the recommended symptomatic treatment. Abdominal pain and cramps are a frequent problem in the adult population, estimated to occur in up to 30% of the population. They are considered a functional gastrointestinal tract disorder and are effectively controlled using antispasmodic agents.

Butylscopolamine is also effective as an analgesic in the treatment of renal colic due to its ability to control the intense colicky pain associated with this condition. The benefit of using Butylscopolamine in the control of non-specific abdominal colic is clinically manifested in the improvement/resolution of the spasms/cramps perceived by the patient, so it is also recommended for treating the irritable bowel syndrome [5, 6]. Finally, it is considered useful in some invasive diagnostic procedures performed on the gastrointestinal tract, such as colonoscopy and sigmoidoscopy.

Clinical evidence

The butyl-bromide derivative of Scopolamine has been used for more than half a century all over the world and has found a widespread application as spasmolytic agent. Evidence of its effectiveness is the regular doctor’s recommendation and the high patient compliance. Several clinical trials have also recently been performed to strengthen the scientific base for its efficacy and tolerability.

Anti spasmodic

Butylscopolamine has been studied in patients with non-specific abdominal pain in several recent studies. One of the most recent large studies compared the efficacy and tolerability of oral Butylscopolamine 10 mg given three times a day to patients with recurrent crampy abdominal pain. A total of 1637 patients were all given a week of placebo, then randomized to three weeks of treatment. Pain intensity (as measured on the Visual Analogue Scale and the Verbal Rating Scale) decreased in all treatment groups, by statistically significant amounts, in comparison with the placebo [7].

Tytgat et al. published two reviews on the use of oral/enteral Butylscopolamine specifically for the treatment of abdominal pain and cramps in a number of clinical scenarios. The drug was considered beneficial in all the trials conducted. The author concluded that the drug’s rapid action and efficacy, together with its high tolerability, support its use in a number of applications ranging from the treatment of acute abdominal spasm, labour and palliative care to support for diagnostic and therapeutic abdominal procedures, in which spasms may be proven to be a problem [8,9].

There is plenty of clinical evidence of the efficacy of Butylscopolamine in the treatment of other specific spasmodic syndromes like IBD (Irritable Bowel Disease) [10,11] and Renal Colic [12,13].

Dysmenorrhea

Two recent studies were conducted to assess the effect of Butylscopolamine on primary and secondary dysmenorrhea in combination with NSAID (Non-Steroidal Anti-inflammatory Drugs) in comparison with a placebo. In both studies the treatment arm showed a consistent decrease in subjective pain intensity score and was significantly more effective than the placebo in providing satisfactory relief [14,15].

Technical Description
Name of the plant Duboisia leichhardtii
Part of the plant Used Leaves
Formula C21H30BrNO4
IUPAC Name [7(S)-(1α,2β,4β,5α,7β)]-9-butyl-7-(3-hydroxy- 1-oxo-2-phenylpropoxy)-9-methyl-3-oxa- 9-azonitricyclo[3.3.1.0(2,4)]nonane bromide
Synonyms 1S, 3S, 5R, 6R, 7S, 8R)-6, 7-epoxy-8-butyl-3-[(S)-tropoyloxy] tropanium bromide. Scopolamine N-Butylbromide. N-Butylscopolammonium Bromide
Molecular Weight 440,40 g/mol
CAS N. 149-64-4

Structural Formula
Butylscopolamine

Bibliografic References
  1. Duboisia myoporoides: The Medical Career of a Native Australian Plant. Historical Records of Australian Science, 200617 (1) 31 – 69. Contribution to the Flora of Australia 1867, p. 94. Paul Foley William Woolls.
  2. Hyoscine butylbromide potently blocks human nicotinic acetylcholine receptors in SH-SY5Y cells. Neurosci Lett. 2009 Feb 6;450(3):258-61. Epub 2008 Dec 6. Weiser T, Just S.
  3. Electrical and mechanical effects of hyoscine butylbromide on the human stomach: a non-invasive approach. Physiol Meas. 2009; 30(4):363–70. Américo MF, Miranda JR, Corá LA, Romeiro FG.
  4. Pharmacotherapy Update: Hyoscine Butylbromide in the Treatment of Abdominal Spasms Clinical Medicine: Therapeutics 2009:1 647–655 Leslie A. Samuels
  5. Hyoscine butylbromide: a review of its use in the treatment of abdominal cramping and pain. Drugs. 2007;67(9):1343-57. Tytgat G N.
  6. Meta-analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome Aliment Pharmacol Ther 2001; 15: 355±361. T. Poynard, C. Regimbeau & Y. Benhamo
  7. Placebo- and paracetamol-controlled study on the efficacy and tolerability of hyoscine butylbromide in the treatment of patients with recurrent crampy abdominal pain. Aliment Pharmacol Ther 23, 2006 _1741–1748. S. Mueller-Lissner*, G. N. Tytgat_, L. G. Paulo_, E. M. M. Quigley§, J. Bubeck–, H. Peil–& E. Schaefer.
  8. Hyoscine butylbromide: a review of its use in the treatment of abdominal cramping and pain. Drugs. 2007;67(9):1343–57. Tytgat GN
  9. Hyoscine butylbromide—a review on its parenteral use in acute abdominal spasm and as an aid in abdominal diagnostic and therapeutic procedures. Curr Med Res Opin. 2008. Tytgat GN.
  10. Meta-analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome. Alimentary Pharmacology & Therapeutics, 15: 355–361. doi: 10.1046/j.1365- 2036.2001.00937.x . 2001 Poynard, T. , Regimbeau, C. and Benhamou, Y.
  11. Pharmacologic treatment of the irritable bowel syndrome: a systematic review of randomized, controlled trials. Ann Intern Med. 2000 Jul 18;133(2):136-47. Jailwala J, Imperiale TF, Kroenke K.
  12. Comparative efficiency study, safety and usage of tested drugs in patients with renal colic. Med Arch. 2006; 60 (6 Suppl 1):37–40. Prcic A, Aganovic D, Junuzovic D, Kulovac B.
  13. Double-blind study with dipyrone versus tramadol and Butylscopolamine in acute renal colic pain. World J Urol. 1994;12(3):155–61. Stankov G, Schmieder G, Zerle G, Schinzel S, Brune K.
  14. Antispasmodic/analgesic associations in primary dysmenorrhea doubleblind crossover placebo-controlled clinical trial. Int J Clin Pharmacol Res. 2001;21(1):21–9. de los Santos AR, Zmijanovich R, Pérez Macri S, Martí ML, Di Girolamo G.
  15. Analgesic-antispasmodic effect and safety of lysine clonixinate and L-hyoscinbutylbromide in the treatment of dysmenorrhea. Ginecol Obstet Mex. 1998;66:35–9. Hernández Bueno JA, de la Jara Díaz J, Sedeño Cruz F, Llorens Torres F.
  16. Tox: Source Document BPI No.: 0057-06 dated 18.10.10 and 0038-06 dated 18.10.2010.

 

scopolamine