Almotriptan Malate

Almotriptan malate showed low nanomolar affinity for human 5-HT(1B) and 5-HT(1D) receptors in radioligand binding assays, while affinity for other 5-HT receptor subtypes including 5-HT(1A) and 5-HT(7) was approximately 40 to 60 times lower. The compound did not exhibit significant affinity for more than 20 non-5-HT receptors studied at concentrations up to 100 μM. In functional assays using HeLa cells transfected with human 5-HT(1B) or 5-HT(1D) receptors, almotriptan inhibited forskolin-stimulated cyclic AMP accumulation with the same efficacy as serotonin and an affinity in the low nanomolar range, behaving as a full agonist. In isolated dog saphenous veins, almotriptan elicited concentration-dependent contractions with an EC50 of 394 nM. Infusion of almotriptan into porcine meningeal vasculature induced vasoconstriction of cranial arteries. In contrast, the compound showed very low maximal efficacy in pig renal and rabbit mesenteric arteries even at 100 μM, indicating selectivity for the cranial vasculature over peripheral vessels.

Fig. 1 Comparison of drug potency and efficacy values obtained in isolated blood vessels. (Bou J.; et al. 2000)

Almotriptan malate-loaded cubosomal in situ gel was developed for intranasal brain targeting to improve blood-brain barrier permeation with rapid onset of action. Cubosomes were prepared using glyceryl monooleate and Pluronic F127 via emulsification-homogenization optimized by Box-Behnken design. The optimized formulation exhibited particle size of 177 nm, polydispersity index of 0.36, zeta potential of -21 mV, and entrapment efficiency of 72.58 percent. The 18 percent Pluronic F127-based in situ gel displayed pseudoplastic rheology with phase transition at nasal temperature. In vitro drug release reached 90.69 percent after 5 hours with a 2.52-fold enhancement in ex vivo permeation compared to plain gel. Histopathology confirmed no nasal mucosa toxicity.

Fig. 2 Almotriptan Malate-loaded cubosomal in situ gel for nanosized intranasal delivery. (Desai G N.; et al. 2023)