Narcolepsy pharmacology

Nishino, S. Mignot, E. (1997). Pharmacological aspects of human and canine narcolepsy. Prog. Neurobiol. 52, 27-78. 

Modafinil (Provigil). The newest stimulant, modafinil, is not, pharmacologically, a true stimulant. Nevertheless, it is an effective treatment for narcolepsy at doses from 200 to 400mg/day. Several studies indicate that modahnil has little potential for abuse and is easier to tolerate than other stimulants. Modafinil has been studied in the treatment of ADHD. Though not approved for marketing by the FDA at the time of this writing, it may gain the indication in the near future. 

GHB was hrst synthesized in the laboratory by the French biochemist Henri Lahorit (1914-1995) in 1961. In the succeeding four decades, extensive research has been conducted on the pharmacological uses and effects of GHB. In general, those studies appear to suggest that GHB has some valuable applications in the medical sciences. It functions well as an anesthetic with apparently few or no serious side effects. Based on this research, the drug has been adopted in many parts of the world for use as a general anesthetic, a treatment for narcolepsy and insomnia, a treatment for alcoholism, and an aid in childbirth. 

Figure 25-8 Baseline separation of enantiomers of the drug Ritalin by HPLC with a chiral stationary phase. One enantiomer is pharmacologically active for treating attention deficit disorder and narcolepsy. The other enantiomer has little activity but could contribute to undesired side effects. Pharmaceutical companies are moving toward providing enantiomerically pure drugs, which could be safer than mixtures of optical isomers. [From R. Bakhtiar, L Ramos, and F. L. S. Tse, "Quantification of Methylphenidate in Plasma Using Chiral Uquid-Chromatography/Tandem Mass Spectrometry Application to Taxicokinetic Studies," Anal. Chim. Acta 2002, 469.261.]...

McClellan KJ, Spencer CM. Modafinil a review of its pharmacology and clinical efficacy in the management of narcolepsy. CNS Drugs 1998 9(4) 311-324. 

On the other hand, pharmacological wake promotion is a new concept brought about by modafinil. Use of modafinil for medical conditions other than narcolepsy has begun to receive the attention of both basic and applied researchers and physicians caring for these patients. Moreover, modafinil consumption is envisioned by some as logical for some critical occupational situa-... 

The approval of armodafinil marked a significant advance in the treatment of narcolepsy. In this chapter, the pharmacological profile and syntheses of modafinil 4 and armodafinil 1 are profiled in detail.16... 

Methylphenidate (MPH, Ritalin ) is a central nervous system stimulant that is used for the treatment of attention deficit disorders, with and without hyperactivity, and narcolepsy. MPH has two chiral centres and is marketed as a racemic mixture. It is known that d-threo-MP is pharmacologically more active than l-threo-MPH. The drag is rapidly metabohzed in humans to the inactive ritalinic acid. High-throughput analysis with chiral selectivity is demanded for the bioanalysis of MPH and its major metabolite. 

The basic pharmacological action of Ephedrine is that of a sympathomimetic. It does not contain a catechol moiety and is effective after oral administration. The drug stimulates heart rate and cardiac output and variably increases peripheral resistance as a result, ephedrine usually increases blood pressure. Stimulation of the a-adrenergic receptors of smooth muscle cells in the bladder base may increase resistance to the outflow of urine. Activation of S-adrenergic receptors in the lungs promotes bronchodilation. Ephedrine stimulates the cerebral cortex and subcortical centers to produce its effects in narcolepsy and depressive states. 

Amphetamine and methamphetamine (Figure 34-19) are CNS stimulant drugs that have limited legitimate pharmacological use. ° They are used to treat narcolepsy, obesity, and attention-deficit hyperactivity disorders. However, they produce an initial euphoria and have a high abuse potential. Other sympathomimetic amines that also have high potential for abuse include the designer amphetamines, ephedrine, pseudoephedrine, phenylpropanolamine, and methylphenidate (Ritalin). 

Doses of medications used to treat narcolepsy are summarized in Table 71-5. Pharmacologic management of narcolepsy is focused on two primary areas treatment of excessive daytime sleepiness (EDS) and treatment of cataplexy. 

The primary objective of pharmacologic treatment of narcolepsy is to reduce symptoms that adversely impact the quality of life. This includes alleviating daytime sleepiness with modaflnil or stimulants. The goal is to produce the fullest possible return of normal function for patients at work, school, home, and socially. Cataplexy, hypnagogic hallucinations, and sleep paralysis should be treated when they are present and troublesome. The health care provider should consider... 

The fact that P(3HB-co-4HB) and P(4HB) are also polymers with potential therapeutic applications has been pointed out in a review [6]. The 4HB units are pharmacologically active compounds, which have been used in the treatment of alcohol withdrawal syndrome [239,240] and narcolepsy [241]. Other potential applications include the treatment of patients with chronic schizophrenia, catatonic schizophrenia, atypical psychoses, chronic brain syndrome, neurosis, drug addiction and withdrawal, Parkinson s disease and other neuropharmacological illnesses, hypertension, ischaemia, circulatory collapse, radiation exposure, cancer and myocardial infarction [242]. 

---