It's a knockout
Knocking a victim out by various means is a staple plot device but it's not as easy as it seems. Physical or chemical methods can be used but it is easy to overlook the problems and unintended consequences. Anaesthetics, after all, is a highly specialised branch of medicine.
A blow on the head?
A blow on the head can be effective but anyone recovering from such a blow, assuming they have not succumbed to a fatal skull fracture, is likely to suffer concussion and be confused and woozy for some time. Also, there is a serious risk of a bleed in the brain (haematoma) which could prove fatal without rapid treatment. This may not appear immediately.
In the neck
Strangling someone to render them unconscious is fraught with dangers, not the least being the risk of the victim stopping breathing altogether. Accidental compression of the vagus nerve in the neck can stop the heart (see, for instance, Cover Her Face by P.D.James). Some judo holds (otherwise known as blood chokes) involve compressing the carotid arteries to produce unconsciousness. Ten seconds compression can produce unconsciousness but prolonged force can result in brain damage and even death. See Kathy Reichs' The Bone Collection and Michael Rowbotham's Close Your Eyes for examples in fiction.
Through the roofies
Rohypnol, or roofies, (flunitrazepam) added to a drink is effective at producing confusion, sleepiness, unconsciousness and amnesia. Traces are eliminated from the body moderately quickly but can be detected some days later if the correct technique is used. If the victim dies shortly afterwards the metabolite (product formed by biochemical action in the body) would be found after a few hours, rather than the drug itself. GHB (gamma hydroxybutyrate) is another "date rape" drug added to drinks for nefarious purposes and this, too, disappears from the body rapidly - from the blood in around four hours and from the urine in twelve. See also Hanging around in the Poisons section for information on residues.
Not a breakfast cereal
Ketamine (also known as "Special K" among other names) is a short-acting anaesthetic drug used in hospitals and by vets. It is a "dissociative" anaesthetic which means patients feel detached from reality - and from pain. C.J. Carver's Spare me the truth includes a good description. Ketamine causes hallucinations, which is why it is used recreationally, and in larger doses produces unconsciousness. Like Rohypnol and GHB, it has been used as a "date rape" drug because of the confusion and amnesia which it causes. As with all drugs, the speed of onset of the effects depends on the route of absorption as well as the dose. Anaesthesia lasting for five to ten minutes can occur in around 30 seconds when the drug is injected into a vein but if it is injected into a muscle it usually take 3-4 minutes and lasts 12-25 minutes. Dissociative effects occur between five and thirty minutes after swallowing ketamine and adverse psychological effects can persist for some time after ketamine has been used, medically or otherwise. Illicit supplies normally come from thefts rather than clandestine manufacture. For more information, with a U.S. slant, see the various entries on ketamine at https://www.drugs.com .
Spicing it up
Synthetic cannabis analogues, known as spice, are powerful disorientating agents. While not anaesthetics they can render someone sufficiently "out of it" to enable a villain to kidnap the victim who would appear drunk and be incapable of resisting - spice has been called the zombie drug because of its incapacitating effects. The material is usually dissolved in solvents and sprayed onto plant material and smoked for recreational use but it could be sprayed onto a normal cigarette or mixed into food for nefarious purposes.
Not to be sniffed at
Chloroform is an old favourite but it takes at least five minutes of inhalation to render someone unconscious and continuous exposure must be maintained if the victim is to stay asleep. A shorter exposure can cause confusion and dizziness but the cliché of a chloroform-soaked rag pressed over someone's face and their falling fast asleep for a prolonged period just doesn't work. Chloroform is no longer used in anaesthesia and modern inhalation anaesthetics require specialist equipment when used. It is a restricted substance and not generally available to the public although it does have some industrial uses.
Not just a prick
Midazolam, often used as an intravenous anaesthetic, is becoming popular in crime fiction but there are often mistakes in administration. To produce rapid unconsciousness the drug must be injected into a blood vessel, in which case the victim would fall asleep quickly - although not instantaneously. Injecting midazolam into the muscles in the back of someone's neck would take considerably longer (around 15 minutes) - assuming you could get enough material into the victim's tissues before they turned round and thumped you. Intravenously, however, effects are likely to occur within half a minute. A prick in the neck followed by instant unconsciousness is simply not realistic.
Propofol, another intravenous anaesthetic, can cause unconsciousness within 10-15 seconds when injected correctly. It does not work if taken orally. Needless to say, these drugs are controlled and not available from your local pharmacist.
How to floor a rhino
Immobilon (etorphine plus a tranquilliser) is the drug used in darts to knock out elephants, rhinos and other large mammals in zoos and game parks. It is not used in UK veterinary general practice any more although it has been in the past. Etorphine is incredibly toxic to humans - thirty millionths of a gram are estimated to be fatal to around half the population and for this reason it is always supplied with enough antidote to reverse its effects. This must be given immediately in the case of inadvertent injection. Immobilon is strictly controlled and it would be very difficult for a murderer to get hold of it.
Tranquilliser darts are not used on humans because of difficulties of calculating the effective dose and the time taken for the drug to take effect. Tasers are the usual, generally non-lethal, immobilisation devices used by police forces (and, increasingly, villains in fiction).
Something in the air
A question which has been used in pharmacy degree examinations is along the lines of "What substance would you use to immobilise a gang of hijackers holding hostages on an aircraft". This highlights the impossibility of using "knockout gas" on a group of people in an uncontrolled manner. Correct answers would include reference to the fact that people respond differently to drugs so some hijackers might be affected while others would not; some of the hostages could be killed by too much anaesthetic; ensuring the gas was properly distributed within the aircraft would be impossible; and it would take so long for unconsciousness to develop that the hijackers would realise what was happening and start shooting anyway. In other words, it wouldn't work.
This was demonstrated tragically, in 2002, when Russian special forces from the FSB stormed a Moscow theatre in which Chechen nationalists had taken hostages. The FSB pumped an incapacitating agent into the theatre's ventilation system to disable the Chechens but, sadly, it killed 130 hostages - 16% of those held. The identity of the agent used has not been formally disclosed but experts believe it was a derivative of fentanyl, a highly potent opiate drug. http://www.bbc.co.uk/news/world-europe-20067384).