Microdialysis pharmacokinetic study of scopolamine in plasma, olfactory bulb and vestibule after intranasal administration

Abstract

The purpose of this study was to investigate the microdialysis pharmacokinetic of scopolamine in plasma, olfactory bulb and vestibule after intranasal administration. The pharmacokinetic study of subcutaneous and oral administration was also performed in rats. From the in vivo results, scopolamine intranasal administration can avoid hepatic first-pass effect. T max plasma samples after intranasal administration were significantly faster than oral administration and subcutaneous injection. The relative bioavailability of intranasal administrations was 51.8-70% when compared with subcutaneous injection. Moreover, one can see that in comparison with scopolamine subcutaneous administration, scopolamine intranasal gel and solutions can increased drug target index (DTI) with olfactory bulb 1.69 and 2.05, vestibule 1.80 and 2.15, respectively. The results indicated that scopolamine can be absorbed directly through the olfactory mucosa into the olfactory bulb, and then transported to various brain tissue after intranasal administration, with the characteristics of brain drug delivery.

Ameliorating treatment-refractory depression with intranasal ketamine: potential NMDA receptor actions in the pain circuitry representing mental anguish

“…Intranasal administration has been established as an effective method for drug delivery to the brain 59 via the olfactory system 60 . These studies suggest that intranasally applied ketamine enters the brain through the olfactory system, where the olfactory nerves traverse holes in the cribiform plate into the olfactory bulb, which sits immediately below the vmPFC (Figure 1).…”

Orexin‐A attenuated motion sickness through modulating neural activity in hypothalamus nuclei

“…Intranasal orexin‐A delivery has been reported to be more effective than intravenous administration in terms of receptor binding in mouse brain (Hanson et al, 2004). Pharmacokinetics studies showed that intranasal scopolamine resulted in a rapid increase in plasma drug concentration for both animals and humans (Stankovic et al, 2019; Wei et al, 2016). In contrast, intranasal delivery of orexin‐A rapidly targets the brain with limited blood distribution (Dhuria et al, 2009).…”

“…For intranasal administration in cats, scopolamine, a nonselective competitive muscarinic receptor antagonist, was utilized as a positive control drug in nasal spray form (Klocker et al, 2001; Wei et al, 2016). Scopolamine and orexin‐A were dissolved in 0.9% saline solution and sterile water with the final concentration at 4 and 20 μg·μl −1 , respectively.…”

“…For intranasal administration in cats, scopolamine, a nonselective competitive muscarinic receptor antagonist, was utilized as a positive control drug in nasal spray form (Klocker et al, 2001;Wei et al, 2016).…”

Therapeutic doses of ketamine acutely attenuate the aversive effect of losses during decision-making.

“…While we achieved a similar effect on choice behavior (Figure 2A, 3A), as well as similar plasma concentrations (Figure S8) with a 1 mg/kg IN dose and a 0.5 mg/kg IM dose, an efficacy difference which is likely explained by a difference in bioavailability (Malinovsky et al, 1996; Yanagihara et al, 2003), we observed a marked reduction in ketamine’s side effects on mayor eye movement measures (Figure 5). IN administered ketamine is thought to reach the brain via the olfactory system, through holes in the cribriform plate where the olfactory nerve enters the brain (Patel et al, 2016; Wei et al, 2016), which in turn sits directly below the prefrontal cortex. When used as an antidepressant, this may allow IN administered ketamine to directly reach brain regions where it may have its therapeutic actions.…”