A treatment for senile dementia of the Alzheimer's type comprising administering to the patient a tertiary amine of the formula ##STR1## wherein R.sup.1 is alkyl, alkoxy, alkylthio or dialkylamino hydroxyl, hydrogen, chlorine or fluorine; R.sup.2 is hydrogen, or when R.sup.1 is hydrogen, alkyl, alkoxy, alkylthio, alkylthioamino, hydroxyl, chlorine or fluorine; R.sup.3 is 1 to 2 carbon alkyl; R.sup.4 is 1 to 3 carbon alkyl; R.sup.5 is an optionally branched 3 to 12 carbon alkylene; X is oxygen or ethylene dioxy; and R.sup.6 is optionally branched or cyclic carbon group having less than eight carbons. The preferred compound is secoverine. The administration of secoverine may be used in conjunction with the coadministration of a cholinergic enhancer, for example, in a combination with acetylcholinesterase inhibitors, muscarinic agonists or choline supplement therapy.
A combination of a muscarinic agonist and an inverse agonist of the GABA.sub.A .alpha.5 receptor subtype useful in treating neurodegenerative conditions such as Alzheimer's Disease is disclosed.
Highly potent analogs of (-)-physostigmine are provided which are potent inhibitors of acetylcholinesterase and butyrylcholinesterase. These compounds are useful in treatment of glaucoma, Alzheimer's disease, myasthenia gravis, and organophosphate poisoning.
Rate-controlled transdermal delivery devices are disclosed which utilize an in-line adhesive to maintain the device on the skin and deliver an agent which is a solvent for the in-line adhesive. The initial equilibrated concentration of the agent in the agent reservoir and the adhesive is below saturation and the reservoir comprises the agent dissolved in a solvent with respect to which the rate controlling element of the device is substantially impermeable. In preferred embodiments the initial loading of the agent in reservoir is sufficient to prevent the activity of the agent in the reservoir from decreasing by more than about 50% and preferrably no more than about 25% during the predetermined period of administration; and the thicknesses of the adhesive, rate controlling membrane and reservoir layers are selected so that at least 50% and, preferrably at least 75% initial equilibrated agent loading is in the reservoir layer. The devices are usable to delivery oily non-polar agents which are liquid at body temperatures such as benztropine and secoverine.
An in-line adhesive, useful for transdermal delivery devices comprising a mixture of high and low molecular weighted polyisobutylene having a ratio HMW PIB:LMW PIB in the range of about 5-40:95-60 which is substantially free of plasticizers and tackifiers is disclosed. The adhesive finds particular use as a component of a transdermal delivery device for delivering oily non-polar agents such as nicotine, benztropine, secoverine, dexsecoverine, and arecoline.
Rate controlled transdermal delivery devices are disclosed which utilize an in-line adhesive to maintain the device on the skin and deliver an agent which is a solvent or a plasticizer for the in-line adhesive. The initial equilibrated concentration of the agent in the agent reservoir and the adhesive is below saturation, and the reservoir comprises the agent dissolved in a solvent with respect to which the rate controlling element of the device is substantially impermeable. In preferred embodiments the initial loading of the agent in reservoir is sufficient to prevent the activity of the agent in the reservoir from decreasing by more than about 50% and preferably no more than about 25% during the predetermined period of administration; and the thicknesses of the adhesive, rate controlling membrane and reservoir layers are selected so that at least 50% and preferably at least 75% initial equilibrated agent loading is in the reservoir layer. The devices are usable to deliver agents which are liquid at body temperatures such as benztropine, secoverine, nicotine, arecoline, polyethylene glycol monolaurate, glycerol monolaurate, glycerol monooleate and ethanol, for example.
