The potential for selective phosphodiesterase inhibitors as therapeutic agents was predicted as early as 1977 by Weiss and Hait. This prediction meanwhile has proved to be true in a variety of fields, vinpocetine EHNA BAY 60-7550 Oxindole PDP Inamrinone and Enoximone are used clinically for short-term treatment of cardiac failure. These drugs mimic sympathetic stimulation and increase cardiac output, anagrelide Cilostazol is used in the treatment of intermittent claudication. Pimobendan is FDA approved for use in the treatment of heart failure in animals. PDE3 is sometimes referred to as cGMP-inhibited phosphodiesterase, piclamilast, a more potent inhibitor than rolipram. Luteolin, supplement extracted from peanuts that possesses IGF-1 properties, used to treat atopic dermatitis. PDE4 is the major cAMP-metabolizing enzyme found in inflammatory and immune cells, PDE4 inhibitors have proven potential as anti-inflammatory drugs, especially in inflammatory pulmonary diseases such as asthma, COPD, and rhinitis.
They suppress the release of cytokines and other signals. PDE4 inhibitors may have effects and have recently been proposed for use as antipsychotics. On October 26,2009, The University of Pennsylvania reported that researchers at their institution had discovered a link between elevated levels of PDE4 in sleep deprived mice, treatment with a PDE4 inhibitor raised the deficient cAMP levels and restored some functionality to Hippocampus-based memory functions. Sildenafil, tadalafil and the newer udenafil and avanafil selectively inhibit PDE5 and these phosphodiesterase inhibitors are used primarily as remedies for erectile dysfunction, as well as having some other medical applications such as treatment of pulmonary hypertension. This results in added benefit when given together with NO or statins, recent studies have shown Quinazoline type PDE7 inhibitor to be potent anti-inflammatory and neuroprotective agents. Papaverine, an alkaloid, has been reported to act as a PDE10 inhibitor. PDE10A is almost exclusively expressed in the striatum and subsequent increase in cAMP and cGMP after PDE10A inhibition is a novel therapeutic avenue in the discovery of antipsychotics
Mosapride is a gastroprokinetic agent that acts as a selective 5HT4 agonist. The major active metabolite of mosapride, known as M1, additionally acts as a 5HT3 antagonist and it is recommended to be taken on an empty stomach. In addition to its properties, mosapride exerts anti-inflammatory effects on the gastrointestinal tract which may contribute to some of its therapeutic effects. Mosapride promotes neurogenesis in the tract which may prove useful in certain bowel disorders. The neurogenesis is due to effect on the 5-HT4 receptor where it acts as an agonist. Its common side effects include dry mouth, abdominal pain, headache, malaise, diarrhea, due to the pharmacokinetics of mosapride, it would take 1, 000–3,000 times the therapeutic dose to elicit cardiovascular effects
Drotaverine is an antispasmodic drug, used to enhance cervical dilation during childbirth. It is structurally related to papaverine, is an inhibitor of phosphodiesterase 4. It is available in Asian and Eastern European countries under several brand names, an article from 2013 described the effects from overdose as including vomiting and fatal cardiac toxicity. In 2016, the young Russian chess player Ivan Bukavshin died of an overdose of the drug
European Chemicals Agency
ECHA is the driving force among regulatory authorities in implementing the EUs chemicals legislation. ECHA helps companies to comply with the legislation, advances the safe use of chemicals, provides information on chemicals and it is located in Helsinki, Finland. The Agency, headed by Executive Director Geert Dancet, started working on 1 June 2007, the REACH Regulation requires companies to provide information on the hazards and safe use of chemical substances that they manufacture or import. Companies register this information with ECHA and it is freely available on their website. So far, thousands of the most hazardous and the most commonly used substances have been registered, the information is technical but gives detail on the impact of each chemical on people and the environment. This gives European consumers the right to ask whether the goods they buy contain dangerous substances. The Classification and Packaging Regulation introduces a globally harmonised system for classifying and labelling chemicals into the EU.
This worldwide system makes it easier for workers and consumers to know the effects of chemicals, companies need to notify ECHA of the classification and labelling of their chemicals. So far, ECHA has received over 5 million notifications for more than 100000 substances, the information is freely available on their website. Consumers can check chemicals in the products they use, Biocidal products include, for example, insect repellents and disinfectants used in hospitals. The Biocidal Products Regulation ensures that there is information about these products so that consumers can use them safely. ECHA is responsible for implementing the regulation, the law on Prior Informed Consent sets guidelines for the export and import of hazardous chemicals. Through this mechanism, countries due to hazardous chemicals are informed in advance and have the possibility of rejecting their import. Substances that may have effects on human health and the environment are identified as Substances of Very High Concern 1.
These are mainly substances which cause cancer, mutation or are toxic to reproduction as well as substances which persist in the body or the environment, other substances considered as SVHCs include, for example, endocrine disrupting chemicals. Companies manufacturing or importing articles containing these substances in a concentration above 0 and they are required to inform users about the presence of the substance and therefore how to use it safely. Consumers have the right to ask the retailer whether these substances are present in the products they buy, once a substance has been officially identified in the EU as being of very high concern, it will be added to a list. This list is available on ECHA’s website and shows consumers and industry which chemicals are identified as SVHCs, Substances placed on the Candidate List can move to another list
Alverine is a drug used for functional gastrointestinal disorders. Alverine is a muscle relaxant. Smooth muscle is a type of muscle that is not under control, it is the muscle present in places such as the gut. Alverine acts directly on the muscle in the gut, causing it to relax and this prevents the muscle spasms which occur in the gut in conditions such as irritable bowel syndrome and diverticular disease. Diverticular disease is a condition in which small pouches form in the gut lining and these pouches can trap particles of food and become inflamed and painful. In irritable bowel syndrome, the activity of the gut muscle is lost. The muscle spasms result in such as heartburn, abdominal pain and bloating. By relaxing the gut muscle, alverine citrate relieves the symptoms of this condition, alverine relaxes the smooth muscle in the womb. It is therefore used to treat painful menstruation, which is caused by muscle spasms in the uterus. Alverine capsules are now available in the market, there are two strengths of capsule-60 mg and 120 mg.
The common dosage for adults and children over 12 years is 60–120 mg taken one, alverine is not suitable for those aged under 12 years. Women who are pregnant or breast-feeding should follow the instruction of doctors for the drug, the side effects of alverine include, Difficulties in breathing or shortness of breath, swelling of the face. Yellowing of the whites of the eyes and the skin, as inflammation of the liver has been known to occur, other side effects include, headache, allergic reaction. It was reported that alverine may induce toxic hepatitis, alverine citrate and simeticone has been combined for irritable bowel syndrome therapy, relating to safety and efficacy in the Clinical Trial Phase IV. At week 4, alverine citrate and simeticone group had lower VAS scores of abdominal pain⁄discomfort, the drug was firstly authorized for marketing on 03/06/2014. Marketing authorisation number is PL 08553/0532, marketing authorisation holder Dr. Reddys Laboratories Ltd.6 Riverview Road, East Yorkshire, HU17 0LD, United Kingdom
Zambon is an Italian company that has been operating in the pharmaceutical and fine chemical industry since 1906. Headquartered in Bresso, in the Province of Milan, the company has operations in three continents, South America and Asia. Gaetano Zambon, founder of the group, was born in Malo in the Province of Vicenza on 31 December 1878 and his father Giovanni owned a corn business. Gaetano Zambon studied pharmacy at the University of Padua and graduated in 1902, seeing the potential and growth of the pharmaceutical sector, he decided to sell products directly to pharmacies. The Warehouse distributed basic pharmaceutical products such as bismuth and bicarbonate, in 1908, the two partners established Gaetano Zambon & Co whose shares were divided equally between Gaetano, Silvio Farina and Teodorico Viero. In 1911, the business expanded over the region, forcing them to move to new offices. The outbreak of the First World War slowed business but did not halt it altogether, G. Zambon & Co. had a small plant that produced products for chemists such as Elixir di China, Rheum and an insecticide called ITE.
In 1930, they bought an old fertiliser plant which was to become the company’s new pharmaceutical production facility, the first Synthetic Product Department was established in 1933, completing the pharmaceutical production process from raw material to finished product. In 1937, Gaetano Zambon and Silvio Farina were appointed Knights of the Order of the Crown of Italy and in 1938, after the departure of Teodorico from the company, società Anonima per Azioni, and increasing the number of employees from 100 to 300 within a decade. During the Second World War, the factory suffered heavy bombing on 14 May 1944, the new Zambon plant was opened in September 1946, with the Minister of Foreign Trade, Pietro Campilli in attendance. Pharmaceuticals produced by Zambon were sold abroad, after the Second World War, the first generation of Zambon partners decided to hand over the reins to the younger generation. After parting ways with the Farina branch in 1951 and the Ferraris in 1957, Gaetano Zambon died in 1959 at the age of 81 years, and the company changed its name once more to Zambon SpA.
The company expanded abroad, setting up production facilities and commercial operations. They opened the first production plant in Brazil in 1956 under the name Zambon Laboratorios Farmaceuticos SA, Zambon SA was established in Barcelona, Spain, in 1960 to serve the Iberian Peninsula. In 1961, Alberto Zambon moved the headquarters and research laboratories to Bresso, Milan. In 1963, Inpharzam was founded in Lamone, which served as a group for all the international businesses. This branch moved to Cadempino, where a specialist pharmaceutical production plant was established, davizam SA, Siphar and the Inpharzam Trading Company SA were established in Lugano. Founded in the year, Zambon France focused on sales and exports to Africa