Delta-8 is a selective octreotide analog that inhibits the growth of neuroendocrine tumors. It has been extensively investigated as a treatment for those with non-functioning pituitary adenomas, carcinoid tumors, and medullary thyroid cancers.
In order to produce products for use in endocrinology and gastroenterology, various modifications at the lipid moiety and amino acid residue were made to the original compound (L-Phe-octreotate). Delta 9 octreotide acetate (trade name Sandostatin) was an early example – it has a wider therapeutic window than L-Phe-octreotate but lacks oral bioavailability due to poor absorption from the. As such, its only use is in hospital injectable form.
In contrast, the original delta 8 online was extensively investigated and found to have a greater effect in inhibiting pituitary cell growth but limited therapeutic window due to a narrow margin between its efficacy at inhibition and toxicity in higher doses causing severe abdominal discomfort, diarrhea and steatorrhoea. Novartis, therefore, developed a definition of octreotide acetate (trade name Sandostatin LAR) which has increased bioavailability by having the amino acid D-Lysine added to the N-terminus of the peptide chain (the other product is Octreotide Acetate Injection which contains only L-Phe, trade name Sandostatin). As the activity of this agent is due to binding with somatostatin receptors on tumor cells, D-Lysine addition caused it to bind less tightly to its target receptor. Apparently, because of this, there are no significant side effects at higher doses that would inhibit its clinical effectiveness in treatment for functional non-functioning pituitary adenomas.
Delta 9 octreotide acetate (trade name Sandostatin) was an early example – it has a wider therapeutic window than L-Phe-octreotate but lacks oral bioavailability due to poor absorption from the gastrointestinal tract. As such, its only use is in hospital injectable form.
In contrast, the original delta 8was extensively investigated and found to have a greater effect in inhibiting pituitary cell growth but limited therapeutic window due to a narrow margin between its efficacy at inhibition and toxicity in higher doses causing severe abdominal discomfort, diarrhea, and steatorrhoea. Novartis, therefore, developed a definition of octreotide acetate (trade name Sandostatin LAR) which has increased bioavailability by having the amino acid D-Lysine added to the N-terminus of the peptide chain (the other product is Octreotide Acetate Injection which contains only L-Phe, trade name Sandostatin). As the activity of this agent is due to binding with somatatin receptors on tumor cells, D-Lysine addition caused it to bind less tightly to its target receptor. Apparently, because of this, there are no significant side effects at higher doses that would inhibit its clinical effectiveness in treatment for functional non-functioning pituitary adenomas.
Pharmacodynamics of octreotide acetate include inhibition of growth hormone secretion, reduction in splanchnic blood flow, and suppression of insulin and glucagon secretion. A major drawback with the use of the original agent was severe adverse gastrointestinal effects including diarrhea, gallbladder contraction resulting in biliary pain, or even pancreatitis in some patients after multiple injections.
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