Methoxyflurane is an inhalation anesthetic. Methoxyflurane was used for surgical, obstetric, or dental anesthesia, but was withdrawn from US market due to safety concerns, but is still in use in Australia and other countries. Methoxyflurane induces muscle relaxation and reduces pains sensitivity by altering tissue excitability by decreasing the extent of gap junction mediated cell-cell coupling and altering the activity of the channels that underlie the action potential.

Floctafenine is an analgesic agent used for the treatment of pain. The drug exerts its anti-inflammatory action by inhibiting COX-1 and COX-2, with a slight preference towards COX-1. Floctafenine is marketed in Canada under the name Floctafenine and it is withdrawn in Europe (Idarac Brand name).

Nefopam (nefopam hydrochloride) is a potent, rapidly-acting non-narcotic analgesic. It is totally distinct from other centrally-acting analgesics such as morphine, codeine, pentazocine and propoxyphene. Unlike the narcotic agents, nefopam (nefopam hydrochloride) has been shown not to cause respiratory depression. It is indicated for the relief of acute and chronic pain, including post-operative pain, dental pain, musculo-skeletal pain, acute traumatic pain and cancer pain. Its mechanism of action is unclear.

Viminol is an opioid analgesic developed by the company Zambon. It is marketed under tradename Dividol for the treatment of pain due to various causes, including the treatment of pain due to osteoarthritis, neuritic pain, vascular pain, visceral pain, neoplastic pain, and pain due to other sources. In vivo studies demonstrated that the analgesic effects of viminol depend on the stereo configuration: the R,R-enantiomer exhibit agonistic activity, while the S,S-enantiomer produce the opposite effect.

1,6-Dimethyl-3-carbethoxy-4-oxo-6,7,8,9-tetrahydro-homopyrimidazol (rimazolium, MZ-144) is an analgesic (non-narcotic). It proved to be effective in all the analgesic assays used (independently of the nociceptive stimulus applied) (hot plate, tail flick, writhing tests, Randall-Selitto test, tail clip, surgical pain) differing in this respect from the nonsteroidal antiinflammatory analgetics. Rimazolium lacks the capacity of producing opiate-like physiological dependence. Also rimazolium fails to show any indication of narcotic-like abuse liability by any of clinical assessments. Rimazolium is registered in Hungary under the brand name Probon. In Hungary among analgesics Probon is the first of choice especially in case of chronic pain accompanying chronic respiratory tract diseases.

Flupirtine is a triaminopyridine derivative having a chemical structure - 2-amino-3-ethoxy-carbonylamino-6-4-fluoro-benzylamino-pyridine. The basic molecule used for synthesis of flupirtine was 2, 6-dichoro 3-nitropyridine. It was first synthesized in 1980s in Germany and was marketed by Degussa Pharma. Flupirtine is a centrally acting, non-opioid analgesic that is available in a number of European countries for the treatment of a variety of pain states. The therapeutic benefits seen with flupirtine relate to its unique pharmacological properties. Flupirtine displays indirect NDMA receptor antagonism via activation of potassium channels and is the first representative of a pharmacological class denoted the 'selective neuronal potassium channel openers'. The generation of the M-current is facilitated by flupirtine via the opening of neuronal Kv7 potassium channels. The opening of these channels inhibits exaggerated neuronal action potential generation and controls neuronal excitability. Neuronal hyperexcitability is a physiological component of many pain states such as chronic pain, migraine and neurogenic pain.

Glafenine is a non-steroidal anti-inflammatory drug (NSAID). Glafenine was withdrawn due to the risk of anaphylaxis and acute kidney failure.

Ziconotide (PRIALT; SNX-111) is a neuroactive peptide, which was approved by FDA in 2004 for the management of severe chronic pain in adult patients for whom intrathecal therapy is warranted, and who are intolerant of or refractory to other treatment, such as systemic analgesics, adjunctive therapies, or intrathecal morphine. Ziconotide acts as a selective N-type voltage-gated calcium channel blocker, which leads to a blockade of excitatory neurotransmitter release from the primary afferent nerve terminals.