Proglumide exhibits delta opioid agonist properties.

Recently, it was reported that proglumide, a cholecystokinin (CCK) antagonist, potentiates the analgetic effects of morphine and endogenous opioid peptides and reverses morphine tolerance by antagonizing the CCK system in the central nervous system of the rat. In order to provide additional insight into the mode of action of this agent, we assessed the effect of proglumide in the isolated guinea pig ileum and the mouse, rat and rabbit vas deferens. Furthermore, we studied the in vitro binding affinity of this substance to mouse brain synaptosomes. Our results show that proglumide inhibits, dose dependently, the electrically stimulated twitches in the mouse vas deferens and guinea pig ileum, but not in the rat or rabbit vas deferens. The inhibitory action of proglumide on the mouse vas deferens, but not on the guinea pig ileum, is antagonized by naloxone and by the selective delta-antagonist, ICI 174,864, in a competitive fashion. Other CCK antagonists were found to be devoid of such activity on the mouse vas deferens. In vitro binding studies showed that proglumide displaces D-ala-D-[leucine]5-enkephalin (DADLE), a delta agonist, but not ethylketocyclazocine (EKC), a preferentially selective kappa agonist. The effect of proglumide appeared to be elicited presynaptically since it did not alter the norepinephrine-induced contractions of the mouse vas deferens. Our results suggest that proglumide might exert its opiate-like effects by activation of delta-opioid receptors.

Comparative effects of dynorphin A(1-9) pyrrolidine analogs on isolated tissues.

Three dynorphin A(1-9) pyrrolidine analogs were synthesized by substituting isoleucine at position 8 with alanine (Ala), D-alanine (D-ala), and D-leucine (D-leu), and assayed for their effect on electrically induced twitches of the isolated guinea pig ileum and mouse vas deferens. All three dynorphin A(1-9) pyrrolidine analogs caused inhibition of the evoked twitches of the two preparations dose-dependently that was reversed by naloxone. However, the substitution by alanine or D-alanine resulted in a decrease in potency on guinea pig ileum when compared to dynorphin A(1-9) pyrrolidine and substitution by D-leucine caused a considerable loss of potency in both mouse vas deferens and guinea pig ileum. Although these substitutions reduced overall potency, a change of potency ratio towards more delta selectivity resulted.

Opioids and rat erythrocyte deformability.

In previous studies from this laboratory, it was noted that opioids in vitro reduced human red blood cell deformability. The effect was found to be dose-dependent, naloxone reversible and preferentially selective kappa ligands exhibited the highest potency. To extend these findings studies were carried out using rat erythrocytes. The time required for erythrocytes to pass through a 5.0 um pore membrane was determined and used as an index of deformability. Opioids added in vitro produced inhibition of deformability in a dose-dependent, naloxone reversible manner. Injecting naive animals with morphine or nalbuphine also produced dose related reductions in red cell deformability. The degree of inhibition produced by nalbuphine correlated well with its plasma concentrations as measured by high performance liquid chromatography (HPLC). Chronic morphine treatment by pellet implantation resulted in the development of tolerance as evidenced by a loss in the ability of morphine in vitro to inhibit red cell deformability. Addition of naloxone resulted in a decrease in filtration time. Thus, the data confirm and extend previous findings on human red blood cells. In as much as previous data from this laboratory demonstrated that opioids inhibit calcium flux from erythrocytes by inhibiting calcium-ATPase and calcium efflux is necessary for normal deformability, it is concluded that opioids act to reduce red cell deformability by inhibition of the calcium pump.

A longitudinal study of life stress and social support among drug abusers.

A longitudinal study was conducted with 49 clients recently discharged from heroin detoxification programs. Interviews were conducted at monthly intervals for 3 months, and information was gathered on drug use, stressful life events experienced, the availability of social support, and the presence of psychiatric symptomatology. Clients who reentered treatment (i.e., methadone maintenance) reported increasing social support over the 3-month period, decreased their use of heroin and several other drugs, and evidenced decreased depression and anxiety. The remainder of the sample evidenced no significant changes over time. Cross-correlation analysis was applied to the data for males and females, separately. The results suggest that women addicts are especially sensitive to the effects of life stressors and tend to lack the support systems which are available to the males. As a means of coping with stressors, in the absence of support, the female addict appears to "self-medicate" with illegal drugs.

The relative impact of family and social involvement on Chicano mental health.

In a household survey, Chicanos attributed significantly more importance to family relationships than did other ethnic groups. For Chicanos, both family satisfaction and social (other than family) satisfaction correlated highly with psychological well-being. Using multiple regression analysis to control for age and income, it was found that for Chicanos family satisfaction was more predictive of overall well-being and positive affect than was social satisfaction. However, social satisfaction was more predictive of level of negative affect than was family satisfaction. The results suggest that the Chicano family may function primarily to provide a positive environment for its members rather than mitigating the stressful effects of a negative environment.