caffeine. Increased adenosine levels are known to cause depression of spontaneous electrical activity of the neurons, inhibition of neurotransmission, and decreased release of neurotransmitters. Adenosine inhibits respiratory drive by blocking the electrical activity of respiratory neurons. Caffeine, as an adenosine antagonist, stimulates these respiratory neurons causing enhancement of respiratory minute volume. Doxapram Doxapram is an intravenous CNS and respiratory stimulant that is typically used to treat respiratory depression caused by anesthesia or chronic obstructive pulmonary disease. It can also be used as a treatment for neonatal apnea, but it can be dangerous, so caution must be taken. Doxapram has been used to treat respiratory depression in drug overdoses, but is not effective for many drugs. The side effects of doxapram are rare, but with overdose, hypertension, tachycardia, tremors, spasticity, and hyperactive reflexes have been seen to occur. Methylxanthines caffeine and theophylline The naturally occurring compounds caffeine and theophylline are structurally classified as methylated xanthines. Side effects typically seen with the use of xanthines include jitters, over-energetic behavior, and insomnia. Less common side effects can include diuresis, gastrointestinal irritation, and rarely ringing in the ears. At high doses, they can also cause psychological dependence. History After their introduction in the early 20th century, analeptics were used to study the new life-threatening problem of barbiturate overdose. Prior to the 1930s, naturally occurring stimulants such as camphor and caffeine were used in the treatment of barbiturate overdose. Between 1930 and 1960, synthetic analeptics such as nikethamide, pentylenetetrazol, bemegride, amphetamine, and methylphenidate replaced the naturally occurring compounds in treating barbiturate overdose. Recently, analeptics have been turned to the treatment of ADHD due to more efficient ways to treat barbiturate overdoses. One of the first widely used analeptics was strychnine, which causes CNS excitation by antagonizing the inhibitory neurotransmitter glycine. Strychnine is subcategorized as a convulsant along with picrotoxin and bicuculline, though these convulsants inhibit GABA receptors instead of glycine. Strychnine was used until the early 20th century, when it was found to be a highly toxic convulsant. Strychnine is now available as a rodenticide and as an adulterant in drugs such as heroin. The other two convulsants antagonize GABA receptors, but neither is commonly accessible today. Doxapram use is declining in humans, though it is an effective CNS and respiratory stimulant, primarily because of shorter-lasting anesthetic agents becoming more abundant, but also because some research has shown potential side effects in infants. Some studies