In this article we are going to address the topic of Indalpine, which is of utmost importance due to its relevance in today's society. Indalpine has aroused great interest in different areas, since its impact extends to multiple aspects of daily life. It is necessary to delve deeper into this topic in order to better understand its implications and consequences. Throughout this article we will analyze different perspectives and approaches related to Indalpine, with the aim of offering a broad and complete vision that allows the reader to delve into its complexity and significance. Without a doubt, Indalpine is a topic that deserves to be explored and discussed in depth, which is why it is essential to address it in a rigorous and exhaustive manner.
Indalpine (INN, BAN; brand name Upstène; developmental code name LM-5008) is a selective serotonin reuptake inhibitor (SSRI) class drug that was briefly marketed. It was discovered in 1977 by the pharmacologists Le Fur and Uzan at Pharmuka, a small French pharmaceutical firm, who credit Baron Shopsin and his colleagues at NYU-Bellevue/NYU School of Medicine in New York with providing the basis for their work. They were particularly influenced by the series of "synthesis inhibitor studies" carried out by Shopsin's team during the early to mid 1970s, and in particular, the clinical report by Shopsin et al. (1976) relating to PCPA's rapid reversal of antidepressant response to tranylcypromine in depressed patients. This led to an understanding of the role of the monoamine neurotransmitterserotonin (5-hydroxytryptamine, or 5HT) in the therapeutic effects of the available tricyclic and MAOI class antidepressants. The studies led to widespread recognition of a serotonin hypothesis of depression, contradicting theories that promoted the role of norepinephrine.
History
While citalopram and zimelidine were developed in the early 1970s, it was Pharmuka's indalpine that was first to reach the market. Baron Shopsin was recruited as consultant to Pharmuka throughout a research and development process that resulted in the marketing of indalpine in France and then worldwide, in 1982. With FDA approval of Pharmuka's IND submission to conduct clinical studies with indalpine and viqueline, Shopsin carried out and published the first clinical trials with these drugs in depressed outpatients in the U.S. Astra's SSRI zimelidine was marketed within a year (1983), but the next crop of SSRIs didn't become commercially available until the 1986 marketing of fluvoxamine in Belgium by Duphar, followed by approval in the United States later that year. Lilly's fluoxetine (Prozac) was approved in the US in 1987.
Meanwhile, zimelidine had been withdrawn soon after its marketing in 1983 due to the emergence of Guillain–Barré syndrome, a serious neurological disease. With lingering concerns among some Common Market countries and activist groups about the potential of SSRIs to induce adverse effects, and the reported association between indalpine and hematological effects, which emerged in the aftermath of Pharmuka's take over by Rhône Poulenc, indalpine was abruptly taken off the market by Rhône Poulenc. Irish psychiatrist David Healy characterized indalpine as being "born at the wrong time" during a period when "indalpine and psychiatry was under siege" by different interest groups in some of the Common Market countries. In line with indalpine's fate, research and development was halted relating to the 2 other 4-alkyl-piperidine derivatives developed by Pharmuka, viqualine (a serotonin releasing agent) and pipequaline (a GABAA receptorpositive allosteric modulator), both in different stages of development at the time.[citation needed]
Recently, revision of this molecular motif yielded SERT inhibitors with nanomolar and subnanomolar IC50 values.
^Shopsin B, Friedman E, Gershon S (July 1976). "Parachlorophenylalanine reversal of tranylcypromine effects in depressed patients". Archives of General Psychiatry. 33 (7): 811–819. doi:10.1001/archpsyc.1976.01770070041003. PMID133650.
^Shopsin B, Lefebvre C, Maulet C (1983). "Indalpine (LM-5008): An open study in depressed outpatients". Current Therapeutic Research. 34 (1): 239–252.