Pizotifen (INN) or pizotyline (USAN), trade name Sandomigran, is a benzocycloheptene-based drug used as a medicine, primarily as a preventative to reduce the frequency of recurrent migraine headaches. Pizotifen is a serotonin antagonist acting mainly at the 5-HT2A and 5HT2C receptors. It also has some activity as an antihistamine as well as some anticholinergic activity. The main medical use for pizotifen is for the prevention of vascular headache including migraine and cluster headache. Pizotifen is one of a range of medications used for this purpose, other options include propranolol, topiramate, valproic acid and amitriptyline. While pizotifen is reasonably effective, its use is limited by side effects, principally drowsiness and weight gain, and it is usually not the first choice medicine for preventing migraines, instead being used as an alternative when other drugs have failed to be effective. It is not effective in relieving migraine attacks once in progress. Pizotifen has also been reported as highly effective in a severe case of erythromelalgia, a rare neurovascular disease that is sometimes refractory to the other drugs named above. Side effects include sedation, dry mouth, drowsiness, increased appetite and weight gain. Occasionally it may cause nausea, headaches, or dizziness. In rare cases, anxiety, aggression and depression may also occur. Pizotifen is well absorbed from the gastro-intestinal tract, peak plasma concentrations occurring approximately 5 hours after oral administration. The absorption of pizotifen is fast (absorption half life 0.5 to 0.8 hours) and nearly complete (80%). Over 90% is bound to plasma proteins. Pizotifen undergoes extensive metabolism. Over half of a dose is excreted in the urine, chiefly as metabolites; a significant proportion is excreted in the faeces. The primary metabolite of pizotifen (N-glucuronide conjugate) has a long elimination half-life of about 23 hours.

Benzydamine (benzydamine hydrochloride, PHARIXIA®) is a benzyl-indazole having analgesic, antipyretic, and anti-inflammatory effects. It is indicated for the relief of pain in acute sore throat and for the symptomatic relief of oro-pharyngeal mucositis caused by radiation therapy.

Ambroxol, a substituted benzylamine, is an active metabolite of bromhexine, which is itself a synthetic derivative of vasicine, the active principle extracted from the plant species Adhatoda vasica. Ambroxol is an expectorant exerting mucokinetic properties, mucociliary activity, stimulation of surfactant production, anti-inflammatory and antioxidative actions and the local anaesthetic effect. Ambroxol was discovered at and has been manufactured by Dr. Karl Thomae GmbH, a division of Boehringer Ingelheim. The ambroxol patent is expired and the drug is available as a generic product from many different companies. Ambroxol was originally developed by Boehringer Ingelheim as a OTC therapy for respiratory disorders related to excessive mucus. Ambroxol's indication is secretolytic therapy in acute and chronic bronchopulmonary diseases associated with abnormal mucus secretion and impaired mucus transport. Boehringer Ingelheim markets the product under various brand names such as Mucosolvan® and Lasolvan®. Ambroxol was identified and found to be a pH-dependent, mixed-type inhibitor of glucocerebrosidase (GCase). Its inhibitory activity was maximal at neutral pH, found in the endoplasmic reticulum, and undetectable at the acidic pH of lysosomes. The pH dependence of Ambroxol to bind and stabilize the enzyme was confirmed. Ambroxol increases both the lysosomal fraction and the enzymatic activity of several mutant GCase variants. This profile of Ambroxol would allow to bind and stabilize GCase in the endoplasmic reticulum (thus preventing its degradation within endoplasmic reticulum), but without affecting GCase in the lysosomes (thus allowing it to degrade glucosylceramide). Indeed, studies showed that Ambroxol treatment significantly increased N370S and F213I mutant GCase activity and protein levels in fibroblasts originally obtained from Gaucher patients. Gaucher's disease is caused by the deficiency of glucocerebrosidase; ambroxol is a chaperone that acts by binding to and stabilising glucocerebrosidase. Zywie (formerly ExSAR Corporation) and Belrose Pharma are developing ambroxol hydrochloride (BEL 0218) for the treatment of type III Gaucher's disease. .

Lidamidine, also known as WHR-1142A and Lidaral, is an alpha2-adrenergic receptor agonist that inhibits intestinal secretion, reduces intestinal transit, and inhibits smooth muscle contraction. Lidamidine hydrochloride is used to treat diarrhoea and other gastrointestinal disorders. Lidamidine’s intestinal antisecretory effects are mediated through the activation of peripheral alpha-2 adrenoceptors. Lidamidine crosses the blood brain barrier poorly and is therefore devoid of the centrally mediated alpha-2 effects that have limited the use of other alpha-2 adrenoceptor agonists in the intestinal tract.

Carbiphene (etomide, SQ 10,269) is a nonnarcotic analgesic agent for the relief of pain. SQ 10,269 is considered to be a non-addicting analgesic agent indicated for the relief of all types of pain, including post-operative pain and pain associated with chronic and recurrent diseases.

Hymecromone (4-methylumbelliferone) is already approved drug in Europe and Asia where it is used to treat biliary spasm. It is used as choleretic and antispasmodic drugs and as a standard for the fluorometric determination of enzyme activity. The concomitant administration of Hymecromone with products, containing metoclopramide, leads to mutual decrease of their action. Due to a danger of diarrhea with subsequent hypokalemia, Hymecromone should be applied with caution to patients on cardiac glycosides therapy (in these cases the sensitivity to them is increased). Hymecromone can be administered simultaneously with otherspasmolytics and analgesics. Very rare allergic reactions, itching, erythema, rashes; diarrhea which normally disappears by reduction of dose or discontinuance of therapy.

Diloxanide (used in the form of furoate) was developed for the treatment of intestinal amoebiasis. The effectiveness of the drug was proved in clinical trials, however, the mechanism of its action is unknown. The drug is not marketed in the United States, athough it is available in India.

Menthyl lactate is derived from menthol, a compound that comes from peppermint oil, or is made synthetically. Menthol has a natural cooling effect, which makes it useful as a topical analgesic to treat skin irritation, pain, itching or sunburn. Despite its cooling benefits, menthol can be a skin irritant. Like menthol, menthyl lactate is cooling, but it causes less skin irritation than menthol. Menthyl lactate also has a refreshing, minty taste. For this reason, some manufacturers use it as a flavoring ingredient. The compound is recommended for use as a flavor in concentrations of 0.005% to 0.2% and in cosmetic and other external products in concentrations ranging from 0.2% to 2.0%. Menthyl lactate is a known compound available e.g. from Haarmann & Reimer GmbH (Germany) under the name FRESCOLAT, Type ML.

Hydroxytamoxifen (Afimoxifene) is an active metabolite of tamoxifen exerting estrogen receptor modulatory function. In addition, hydroxytamoxifen binds to regulates transcriptional activity of the estrogen-related receptor gamma. ASCEND Therapeutics, Inc. was developing TamoGel (4-hydroxytamoxifen gel) for a variety of estrogen-dependent conditions, including breast cancer, cyclic breast pain and gynecomastia.

Clove oil is a natural product, derived from the Eugenia caryophyllata tree. Clove oil is 85 to 95% eugenol. Isoeugenol and methyleugenol make up 5 to 15% of the remaining ingredients. Isoeugenol is manufactured from eugenol by a process of isomerization. Isoeugenol have been used in foods and eugenol has been used in animal feeds. Isoeugenol is used as a fish anesthetic. The mechanism of action of isoeugenol in fish has not been determined. It is hypothesised that its effects are mediated via receptors controlling cellular ion channels in a similar way to that described for local anaesthetics. Reports of adverse reactions involving the use of isoeugenol in humans are primarily confined to incidents of contact sensitization or allergy following dermal exposure.