6110. Methylphenidate

Nomenclature

CAS number: 113-45-1
α-Phenyl-2-piperidineacetic acid methyl ester; methyl phenidylacetate; methyl α-phenyl-α-(2-piperidyl)acetate; methylphenidan.
C14H19NO2; mol wt 233.31.
C 72.07%, H 8.21%, N 6.00%, O 13.72%.

Description and references

Piperidine derivative related structurally to dextroamphetamine, q.v. Prepn: L. Panizzon, Helv. Chim. Acta 27, 1748 (1944); M. Hartmann, L. Panizzon, US 2507631 (1950 to Ciba). Sepn of isomers: R. Rometsch, US 2957880 (1960 to Ciba). LC/MS/MS determn in dog plasma: R. Bakhtiar et al., Anal. Chim. Acta 469, 261 (2002). Comprehensive description: G. R. Padmanabhan, Anal. Profiles Drug Subs. 10, 473-497 (1981). Pharmacokinetics: N. R. Srinivas et al., Pharm. Res. 10, 14 (1993). Clinical efficacy in attention deficit-hyperactivity disorder (ADHD): W. E. Pelham, Jr. et al., J. Consult. Clin. Psychol. 61, 506 (1993); R. G. Klein, Encephale 19, 89 (1993). Review of pharmacokinetics in ADHD: M. L. Wolraich, M. A. Doffing, CNS Drugs 18, 243-250 (2004); of clinical experience in ADHD and pharmacology of isomers: D. J. Heal, D. M. Pierce, ibid. 20, 713-738 (2006).

Chemical structure

Properties

bp0.6mm 135-137°. Sol in alcohol, ethyl acetate, ether. Practically insol in water, petr ether.

Derivative

Hydrochloride.

Nomenclature

CAS number: 298-59-9
Ciba 4311b; Concerta (Alza); Equasym (UCB); Metadate (UCB); Ritalin (Novartis).
C14H19NO2.HCl; mol wt 269.77.
C 62.33%, H 7.47%, N 5.19%, O 11.86%, Cl 13.14%.

Properties

Crystals, mp 224-226°. pKa 8.9. Freely sol in water, methanol; sol in alcohol; slightly sol in chloroform, acetone. Solns are acid to litmus. D50 orally in mice: 190 mg/kg (See: E. N. Greenblatt, A. C. Osterberg et al., J. Pharmacol. Exp. Ther. 131, 115 (1961)).

Derivative

d-threo-Form.

Nomenclature

CAS number: 40431-64-9
(αR,2R)-α-Phenyl-2-piperidineacetic acid methyl ester; dexmethylphenidate.

Description and references

Enantioselective synthesis: J. M. Axten et al., J. Am. Chem. Soc. 121, 6511 (1999).

Derivative

d-threo-Form hydrochloride.

Nomenclature

CAS number: 19262-68-1
Dexmethylphenidate hydrochloride; Focalin (Novartis).

Description and references

Clinical trials in ADHD: L. E. Arnold et al., J. Child Adolesc. Psychopharmacol. 14, 542 (2004); R. Silva et al., ibid. 555.

Properties

White to off-white powder. Freely sol in water, methanol; sol in alcohol; slightly sol in chloroform, acetone.

Note

This is a controlled substance (stimulant): 21 CFR, 1308.12.

Therapeutic Category

CNS stimulant.

Therapeutic Category (Veterinary)

In treatment of canine behavioral problems.

Keywords

CNS Stimulant