Evaluating the Neurophysiologic and Clinical Effects of Single Dose Drug Challenge

Inclusion Criteria:

• Subjects ages 18-45, with FXS who completed the study entitled "Mechanisms and braincircuits underlying fragile X syndrome" (IRB # 2015-8425) or appropriate baselinemeasures through Biorepository (2013-7327).

• FXS is defined as full FMR1 mutations (>200 CGG repeats) confirmed by genetictesting.

• General good health as determined by physical exam, medical history and laboratorywork up.

• Stanford Binet IQ <85

• Stable dosing of psychotropic drugs for at least 4 weeks.

Exclusion Criteria:

• Subjects with a history of intolerance to baclofen, roflumilast, or memantine willbe excluded.

• Subjects will also be excluded if they have taken any investigational drug within 3months, have a history of substance abuse or dependence within 6 months, orsignificant psychiatric or CNS neurological disease unrelated to FXS.

• Uncontrolled seizures or history of epilepsy with a seizure in the past 6 months

• Auditory or visual impairments that cannot be corrected based on visual and auditoryscreener benchmarks.

• Moderate to severe renal or hepatic impairment and determined by a study physicianincorporating data from exam, medical history and laboratory value evaluation amongother data points.

• Use of barbiturates, benzodiazepines, antiepileptics, or other GABAergic orglutamatergic modulators

• Current use of: Amifampridine, Butalbital, Codeine, Doxylamine, Ethanol,Hydrocodone, Isocarboxazid, Kava, Metoclopramide, Midazolam, Oxybate, Phenelzine,Promethazine, Thalidomide, Tranylcypromine, Trimethobenzamide, Erythromycin,Ketoconazole, Fluvoxamine, Enoxacin, and Cimetidine.

• Those taking other psychiatric medications must be on stable doses for 4 weeksbefore the baseline visit.

• Pregnancy or breast-feeding. For female subjects of child bearing potential, a urinepregnancy test will be performed.

• Potential subjects with a creatinine clearance < 50 mL/min will be excluded.

• Identified medical issues, inability to tolerate study procedures or study drug perthe discretion of the Principal Investigator.