Bornaprine was first synthesized in 1960 by theGermanscientist H Haas, under the name Kr 399.[4][5][6] Additional tests revealed that bornaprine was significantly more effective than nicotine at antagonizing choline.[4][5][6] Because of its anticholinergic effects, it was intended to help with thesymptoms of Parkinson's.[7] Early clinical trials with Parkinsonian patients (completed in Germany), showed that bornaprine was successful at treating many of the key side-effects of Parkinson's includingakinesia,language,tremors, andpsychological symptoms.[7]
Bornaprine is successfullyabsorbed into theplasma ofhumans within 1–2 hours after anoraldose.[13] Additional oral doses of bornaprine resulted in some accumulation in the plasma.[13]
Single oral doses of bornaprine were successfullyexcreted in urine and feces inrats,dogs, and humans.[13] The following mean excretion rates were also reported during five days for urine and feces: rat 31 and 70%, dog 53 and 39%, and humans 78 and 4%.[13] Excretion was notably prolonged and incomplete at five days in humans, indicating a longer half life and metabolism rate of bornaprine for humans.[13] In human subjects, bornaprine has a half life of approximately 30 hours compared to 5 and 12 hour half lives in rats and dogs, respectively.[13]
Bornaprine is an epimeric mixture ofexo and endoesters, and its majormetabolites have been identified and include: threeisomers of monohydroxy-N-desthel-sormodren, three isomers of monohydroxy-sormodren and 5-hydroxyl.[13] Each of these metabolites were hydroxylated at either C-5 or C-6 in the bicyclic ring.[14] The activity of each ofcompounds has been studied extensively and 5-hydroxyl showed similar anticholinergic activity to the parent compound when tested in isolated rat atrium unlike other identified metabolites.[12]
Bornaprine is currently available under the brand name Sormodren in the following countries: Austria (Abbott Pharmaceuticals), Germany (Abbott), Italy (Teofarma Pharmaceuticals), and Turkey (Abbott). Bornaprine is normally administered in atablet form, however a recentpatent is investigating the effect of several anticholinergic drugs, including bornaprine, in transdermalpatches. These patches are not currently available to the public market. Bornaprine is not currently on the market in the United States and its clinical trial status is unknown.
Like many other anticholinergic drugs, bornaprine had been used to treat the symptoms of Parkinson's disease. Bornaprine most effectively treats the tremors associated with Parkinson's and also helpsbradykinesia,hypokinesia, andposture andfacial expression.[1]
Hyperhidrosis occurs in acute phase ofspinal cord injured patients and an effective oral treatment for hyperhidrosis has yet to be perfected.[3] A recent study done with patients withmedullarylesions found bornaprine to be very effective in decreasing the amount ofsweating in patients with minimalside-effects.[3] Bornaprine is now commonlyprescribed for treating hyperhidrosis inEurope.
When administered to healthy humans, bornaprine suppressed the amount ofREM sleep, suggesting that the M1 and M2 receptors are involved insleep increase and REM latency.[10] This also suggests that bornaprine may be able to be used as asleep aid in the future.[10]
Since bornaprine is a potent anticholinergic drug, it has a similar side effect profile to other anticholinergic drugs, includingdry mouth andconstipation.[15][1] Additionally, when bornaprine was administered to patients with secondary parkinsonism, few patients reported transientconfusion.[11]
Bornaprine can be synthesized beginning withatropic acid (2-phenyl acrylic acid,1).[17] ADiels-Alder reaction withcyclopentadiene (2) gives the bicyclic compound3.Catalytic hydrogenation overRaney nickel gives 2-phenylbicyclo[2.2.1]heptane-2-carboxylic acid (5). Conversion of the acid to the acid chloride and esterification with 3-diethylaminopropanol (4) completes the synthesis of bornaprine (6).
^abcCantello R, Riccio A, Gilli M, Delsedime M, Scarzella L, Aguggia M, Bergamasco B (February 1986). "Bornaprine vs placebo in Parkinson disease: double-blind controlled cross-over trial in 30 patients".Italian Journal of Neurological Sciences.7 (1):139–43.doi:10.1007/BF02230432.PMID3514543.
^abHaas H (1960). "3-Piperidino-1-phenyl-1-(bicyclo[2.2.1]hept-5-en-2-yl)-1-propanol (Akineton). II".Archives Internationales de Pharmacodynamie (in German).78: 204–38.
^abHaas H, Wulzinger H (1960). "3-Piperidino-1-phenyl-1-(bicyclo[2.2.1]hept-5-en-2-yl)-1-propanol (Akineton). III".Archives Internationales de Pharmacodynamie Therapy (in German).78: 239–52.
^abHaas H (1964). "Supplementary investigations of the spasmolytic bicyclophenamine (β-pyrrolidinylethyl 2-phenylbicyclo[2.2.1]heptane-2-carboxylate)".Arzneimittel-Forschung (in German).14: 342–7.
^abcAvenarius HJ, Gesterbrandt F (1968). "Kr 339, ein neus tremorhemmendes Praparat zu Behandlung des Parkinson Syndromes".Wien klin Wochenschr (in German) (80th ed.).
^Kreiskott H, Kretzschmar R (1985). "Neuere pharmakologische Aspekte zu den zentralen Anticholinergika Biperiden und Bornaprin".Das Parkinson-Syndrom (in German). pp. 277–87.
^abSancesario G, Cicardi MC, Fiermonte G, Giacomini P, Stanzione P (September 1984). "Effectiveness of bornaprine on parkinsonian tremor".Italian Journal of Neurological Sciences.5 (3):289–93.doi:10.1007/bf02043960.PMID6500902.
^abHufford CD, Elmarakby SA, Walker LA (1991). "Anticholinergic activity of bornaprine and its metabolites in the isolated rat atrium".Pharmacology.42 (1):23–7.doi:10.1159/000138764.PMID2057518.
^abcdefgMayo BC, Biggs SR, Chasseaud LF, Hawkins DR, Darragh A, O'Kelly DA (December 1980). "The metabolic fate of Sormodren (bornaprine hydrochloride) in animals and humans".Xenobiotica; The Fate of Foreign Compounds in Biological Systems.10 (12):873–88.doi:10.3109/00498258009033821.PMID7210700.
^Elmarakby SA, Clark AM, Baker JK, Hufford CD (June 1986). "Microbial metabolism of bornaprine, 3-(diethylamino)propyl 2-phenylbicyclo[2.2.1]heptane-2-carboxylate".Journal of Pharmaceutical Sciences.75 (6):614–8.doi:10.1002/jps.2600750620.PMID3735109.
^Bergamasco B, Cantello R, Delsedime M, Gilli M, Riccio A, Aguggia M (October 1985). "[Preliminary open multicenter study on the anti-tremorigenic effectiveness of bornaprine (Sormodren)]".Minerva Medica.76 (40):1877–81.PMID4058785.
^ab"Bornaprine".United States National Library of Medicine. National Institute of Health. Retrieved1 March 2014.[dead link]
