use of specific opioid receptor antagonist [nalthrexone] in hypertensive pregnancy

Twenty pregnant patients induced hypertension in late pregnancy [30-36 weeks] were randomly allocated to either Nalthrexone [R Trexan], specific opioid receptor antagonist, or placebo treatment. Nalthrexone was given in the form of tablets, 50 mg/12 hours. Blood pressure was measured twice daily and measuring of proteinunria was done daily with observation of edema of the lower limbs. The serum levels of prolactin before, one week and 2 weeks after treatment, were measured by radioimmunoassay. This was done also to 51 normal pregnant women in the same gestational age. The results show normalization of blood pressure, subsidence of pretibial edema and minimal decrease in body weight. This was associated with decrease of serum proloctin from 148 +/- 12.8 to 23.4 +/- 4.76 ng/ml after treatment. All babies were delivered at term in a healthy condition. There was no effect on the initiation of lactation which was normal up to 3 months after delivery. The present results of potential value from the clinical and biological points of view are: Nalthrexone is an effective and safe drug to be used in PIH. Beta-endorphin may play a role in the pathogenesis of PIH through controlling the release of prolactin

Participation of opioid receptors in the modulation of the analgesic response by adrenal and gonadal glands

The invovlement of opiodi receptors in the analgesic response was evaluated by the tail-immersion test in simultaneously adrenalectomized and ovariectomized female Wistar rats (210-250g). The reaction time (mean ñ SEM) for tail withdrawal from hot water decreased significantly 2 weeks after surgery (3.52 ñ 0.20 s) when compared to intact animals (6.09 ñ 0.23 s). Hormonal replacement with dexamethasone (50*/day) did not affect reaction time (3.38 ñ 0.19 s). However, this response was restored by combined adrenal and gonadal steroid substitution (estradiol 5*g/day and progesterone 1.5*g 6h before the test) therapy (5.11 ñ 0.45 s) in animal treated with dexamethasone plus estradiol and 5.04 ñ 0.43 s in animals treated with dexamethasone plus estradiol plus progesterone). Naloxone (2mg/Kg decreased the reaction time of animals treated with adrenal and gonadal steroids (5.11 ñ 0.45 vs 4.15 ñ 0.44 and 5.04 ñ 0.43 vs 3.87 ñ 0.28 s, respectively, before and after naloxone) but failed to decrease it in rats treated with dexamethasone only (3.88 ñ 0.18 vs 4.34 ñ 0.25 s, before and after naloxone). These observations indicate that gonadal steroids are the most important steroid factors involved in the reaction time to tail immersion in hot water and confirm other reports that the opioid pathways modulating the neuronal circuitry require the presence of these hormones

Role of endogenous opioids and histamine in morphine induced emesis.

The role of opioid and histaminergic system in morphine induced emesis was investigated in dogs. Morphine (25 micrograms, icv) consistently evoked emesis with an average latency of 195 +/- 29 sec which was fully accounted for by an action on the chemoreceptor trigger zone (CTZ) as its ablation rendered animals refractory to vomiting. Intraventricular pretreatment with opioid antagonist naloxone, histamine H1 antagonist mepyramine and H2 antagonists metiamide and cimetidine afforded protection to icv morphine emesis. The CSF histamine concentration was significantly raised 5 min after icv morphine administration. The results suggest that both endogenous opioid and histamine are involved in morphine emesis. Naloxone in high doses (1600 micrograms, icv) elicited emesis which was not blocked by CTZ ablation confirming our earlier report.