Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, ON, N1G2W1, Canada.
Institute of Drug Research, Medical Facility, Hebrew University of Jerusalem, Jerusalem, Israel.
Psychopharmacology (Berl). 2022 Feb;239(2):377-383. doi: 10.1007/s00213-021-06005-4. Epub 2021 Oct 21.
The fatty acid amide oleoyl glycine (OlGly) and its more stable methylated form oleoyl alanine (OlAla) reduce naloxone-precipitated morphine withdrawal (MWD)-induced conditioned gaping (nausea) responses in rats. In addition, OlGly has been shown to reduce lithium chloride (LiCl)-induced conditioned gaping in rats and vomiting in Suncus murinus (house musk shrews).
Here, we compared the potential of these fatty acid amides to maintain their anti-nausea/anti-emetic effect over a delay. The following experiments examined the potential of a wider dose range of OlGly and OlAla to interfere with (1) LiCl-induced conditioned gaping in rats and (2) LiCl-induced vomiting in shrews, when administered 20 or 70 min prior to illness.
OlAla (1, 5, 20 mg/kg) reduced LiCl-induced conditioned gaping, with OlGly only effective at the high dose (20 mg/kg), with no effect of pretreatment delay time. At the high dose of 20 mg/kg, OlGly increased passive drips during conditioning suggesting a sedative effect. In shrews, both OlGly and OlAla (1, 5 mg/kg) suppressed LiCl-induced vomiting, with no effect of pretreatment delay. OlAla more effectively suppressed vomiting, with OlAla (5 mg/kg) also increasing the latency to the first vomiting reaction.
OlAla was more effective than OlGly in reducing both LiCl-induced gaping in rats and LiCl-induced vomiting in shrews. These findings provide further evidence that these fatty acid amides may be useful treatments for nausea and vomiting, with OlAla demonstrating superior efficacy.
脂肪酸酰胺油酰甘氨酸（OlGly）及其更稳定的甲基化形式油酰丙氨酸（OlAla）可减少纳洛酮诱发的吗啡戒断（MWD）诱导的条件性张口（恶心）反应在大鼠中。此外，OlGly 已被证明可减少氯化锂（LiCl）诱导的大鼠条件性张口和 Suncus murinus（家鼠鼩鼱）的呕吐。
在这里，我们比较了这些脂肪酸酰胺在延迟时间内维持其抗恶心/止吐作用的潜力。以下实验研究了更广泛的 OlGly 和 OlAla 剂量范围在以下情况下干扰（1）LiCl 诱导的大鼠条件性张口和（2）LiCl 诱导的鼩鼱呕吐的潜力，给药时间为疾病前 20 或 70 分钟。
OlAla（1、5、20mg/kg）可减少 LiCl 诱导的条件性张口，而 OlGly 仅在高剂量（20mg/kg）时有效，预处理延迟时间无影响。在 20mg/kg 的高剂量下，OlGly 在条件作用期间增加了被动滴水，提示有镇静作用。在鼩鼱中，OlGly 和 OlAla（1、5mg/kg）均可抑制 LiCl 诱导的呕吐，预处理延迟时间无影响。OlAla 更有效地抑制呕吐，OlAla（5mg/kg）还增加了第一次呕吐反应的潜伏期。
OlAla 比 OlGly 更有效地减少 LiCl 诱导的大鼠张口和 LiCl 诱导的鼩鼱呕吐。这些发现进一步证明，这些脂肪酸酰胺可能是治疗恶心和呕吐的有效方法，OlAla 显示出更好的疗效。
