fMRI-behavioral Study of Cholinergic Augmentation With Donepezil in Healthy Sleep Deprived Adults

Inclusion Criteria: 1. The subject is able to read and understand the Subject Information Sheet and comply with protocol requirements, instructions and protocol-stated restrictions. 2. Prior to any screening procedures, the subject and the physician must have signed a study-specific Informed Consent Form. No study-related procedures may be performed before the physician has obtained written informed consent from the subject. 3. The subject is between 21 years to 35 years of age. 4. The subject has a BMI of between 18.5 kg/m2 to 32 kg/m2 and body weight ≥ 50 kg. 5. The subject is right-handed. 6. The subject has a resting pulse \>40 bpm and \<90 bpm (normal range). The subject has a resting systolic blood pressure of between 91 mmHg to 140 mmHg (supine normal range) and a resting diastolic blood pressure of between 51 mmHg to 90 mmHg (supine normal range). 7. The subject, in the opinion of the investigator, is in good health on the basis of a pre-study physical examination, medical history, vital signs, electrocardiogram (ECG), and the results of blood chemistry, haematology, and serology tests, and a urinalysis. A subject with a clinical abnormality or laboratory parameters outside the reference range for this age group may be included only if the Investigator considers that the finding will not introduce additional risk factors and will not interfere with the study procedures. 8. The subject has habitual good sleeping habits: sleeping on average 6.5 to 9 hours each night in the past month. 9. Have regular sleeping hours whereby they sleep no later than 1 am and rise before 9 am each day. 10. Have no history of excessive daytime sleepiness or insomnia. 11. Score no greater than 22 on the Morningness-Eveningness scale \[Horne and Ostberg, 1976\]. 12. If female, the subject must use a double barrier method of contraception (2 separate methods of contraception) from Screening until final discharge from the study. Oral contraceptives are not allowed. Exclusion Criteria: 1. The subject has taken prohibited medication within 1 week (or 14 days if the drug is a potential enzyme inducer) or within 5 half-lives prior to first dosing for any medication ingested, whichever is longer) prior to first dosing, unless in the opinion of the investigator and sponsor, the medication will not interfere with the study procedures or compromise safety. Prohibited medication is any prescribed medication or over-the-counter (OTC) medication, including high-dose vitamins or dietary supplements, or any herbal medicine known to interfere with the metabolic CYP pathways, (e.g. St. John's Wort) or cognitive function (e.g. ginko). Paracetamol for mild analgesia will be permitted. 2. The subject has a significant history of drug or alcohol abuse, defined as an alcohol intake greater than 21 units per week or a history of drug abuse within the last 6 months, or a history of substance abuse deemed significant by the investigator. A unit of alcohol is defined as 250 mL of lager/beer, 100 mL of Wine, or 25 mL of spirits. 3. The subject has an orthostatic blood pressure reduction \>20 mmHg (based on the difference of systolic blood pressure between supine and after standing for 1 minute). 4. The subject has been exposed to more than 3 new chemical entities (NCEs) within 12 months prior to the first dosing day, or participated in a trial with any drug within 84 days before the start of the study, or participated in a trial with a NCE within 112 days before the start of the study. 5. History or presence of hypersensitivity to the study drugs or drugs of this class (hyoscine, atropine, donepezil) or a history of other severe drug allergy or hypersensitivity which, in the opinion of the physician responsible, contraindicates their participation. 6. The subject has a serious illness, such as liver or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, infectious, neoplastic, or metabolic disturbance or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs. 7. The subject has history or presence of peptic ulcer disease, cardiac arrhythmias, cardiac conduction abnormalities, asthma or obstructive pulmonary disease. 8. The subject has history or presence of psychiatric or neurological illness, obstructive sleep apnea, narcolepsy or periodic leg movements as ascertained by questionnaire. 9. If participation in the study will result in the subject having donated more than 1500 mL blood in the previous 12 months and where participation in study would result in donation of blood in excess of 500 mL within a 56 day period. 10. The subject smokes more than 10 cigarettes per day or uses other nicotine containing products equivalent to 10 cigarettes per day (for example, snuff, nicotine patch, nicotine chewing gum, mock cigarettes, or inhalers) and is not able to refrain from using nicotine containing products during the complete study period. 11. The subject tested positive after screening or at baseline for drugs of abuse (opiates, methadone, cocaine, amphetamines, barbiturates, benzodiazepines, and cannabinoids). 12. Caffeine intake of greater than 5 drinks per day on average. 13. Presence of glaucoma or raised intraocular pressure based on medical history. 14. Has an abnormality on acoustic function. 15. The presence of a cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies. 16. The volunteer reports previous marked feelings of claustrophobia in enclosed environments. 17. Abnormal anatomical MRI as defined by a radiologist on pre-study screening e.g. tumours, evidence of stroke, localized white matter lesions, excessive atrophy (local or global), aneurysms, vascular malformations. 18. Subjects who cannot complete the neuropsychological test battery despite having undergone the training sessions. 19. The subject's QTc (using Bazett's correction) is equal or greater than 430 ms (at Screening) as read on the printout of the ECG produced by the ECG equipment and evaluated by the investigator. 20. The subject, in the opinion of the investigator, is unlikely to comply with the clinical study protocol or is unsuitable for any other reason.