Scopolamine with physostigmine

Meshulam, Y. et al. Prophylactic transdermal treatment with physostigmine and scopolamine against soman intoxication in guinea-pigs, J. Appl Toxicol, 15, 263, 1995. 

Other CMs also have a good prophylactic efficacy, especially physostigmine and aminostigmine (due to their central effect which is contrary to pyridostigmine Tuovinen and Hanninen, 1999 Kim et al., 2002 Tonkopii, 2003). Experimental studies with transdermal administration of physostigmine suggest a serious interest in the prophylactic use of this drug (Levy et al., 1992 Jermer et al., 1995 Walter et al., 1995 Kim et al., 2005 Cho, 2012 Cho et al., 2012). A similar approach was described with scopolamine (Che et al., 2011). 

Drug solutions and implantation of osmotic mini-pumps Physostigmine hemisulphate and procyclidine hydrochlorid were obtained from Sigma (St.Louis, U.S.A.), scopolamine hydrobromid from Merck (Darmstadt, Germany), atropine sulphate was obtained from ACF (Amsterdam, The Netherlands), and diazepam from Roche (The Netherlands). HI-6 was made available by the Defence Research Establishment, Suffield, Canada. Soman (O-pinacolyl methylphosphonofluoridate) was synthesised at TNO. Alzet Osmotic Mini-pumps with a constant delivery rate of 0.55 pl/hr (Model 2002, Alza Corp., Palo Alto, USA) were used to deliver PYR, PHY and SCO. The vehicle consisted of 20% propylene glycol, 10% ethanol and 70% water. The pumps were implanted subcutaneously under isoflurane/02 inhalation anesthesia. 

As an inhibitor of plasma (pseudo) cholinesterase, DFP produced only minimal reversal of scopolamine-induced incapacitation. Note the very low plasma ChE levels, with only minor decreases in RBC ChE (Fig. 71). DFP does improve near vision when applied to the eye (David Flarper, unpublished data) suggesting that paralysis of the muscles of visual accommodation is probably peripheral in origin. Persistence of pupillary enlargement (in the face of systemic treatment with physostigmine) may be due to physiological or pK factors, causing limited access to the iris. 

Solana RP, Gennings C, Carter WH Jr, et al. Efficacy comparison of two cholinolytics, scopolamine and azaprophen, when used in conjunction with physostigmine and pyridostigmine for protection against organophosphate exposure. J Am Coll Toxicol. 1991 10 215-222. 

Crowell EB, Ketchum JS. The treatment of scopolamine induced delirium with physostigmine. Clin Pharmacol Ther. 1967 8 409-414. 

Cholinesterase inhibitors benefit certain patients (Bartus et al, 1982). The central cholinergic blocker, scopolamine, induces memory dysfunction resembling aging and Alzheimer s disease in young, normal subjects. Phy-sostigmine reverses these scopolamine-induced defects in memory and cognition. However, the response is different in patients with Alzheimer s disease the improvements with physostigmine have been erratic and... 

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