Background and Purpose
Vasopressin V1B receptor antagonists may be effective for the treatment of depression and anxiety and the objective of this study was to characterize the pharmacological ...profiles of two newly synthesized arginine vasopressin receptor 1B (V1B receptor) antagonists, TASP0233278 and TASP0390325.
Experimental Approach
We investigated the in vitro profiles of TASP0233278 and TASP0390325. In addition, the effect of TASP0390325 on the increase in plasma adrenocorticotropic hormone (ACTH) levels induced by corticotropin‐releasing factor (CRF)/desmopressin (dDAVP) was investigated. We also investigated the antidepressant and anxiolytic profiles of TASP0233278 and TASP0390325 in animal models.
Key Results
Both TASP0233278 and TASP0390325 showed a high affinity and potent antagonist activity for V1B receptors. Oral administration of TASP0390325 antagonized the increase in plasma ACTH levels induced by CRF/dDAVP in rats, indicating that TASP0390325 blocks the anterior pituitary V1B receptor in vivo. Oral administration of TASP0233278 or TASP0390325 also exerted antidepressant effects in two models of depression (a forced swimming test and an olfactory bulbectomy model). Moreover, TASP0233278 improved depressive‐like behaviour induced by repeated treatment with corticosterone, a model that has been shown to be resistant to treatment with currently prescribed antidepressants. In addition to depression models, TASP0233278 or TASP0390325 exerted anxiolytic effects in several anxiety models (social interaction, elevated plus‐maze, stress‐induced hyperthermia, separation‐induced ultrasonic vocalization and sodium lactate‐induced panic‐like responses in panic‐prone rats).
Conclusion
TASP0233278 and TASP0390325 are potent and orally active V1B receptor antagonists with antidepressant and anxiolytic activities in rodents.
Background and Purpose Vasopressin V sub(1B) receptor antagonists may be effective for the treatment of depression and anxiety and the objective of this study was to characterize the pharmacological ...profiles of two newly synthesized arginine vasopressin receptor 1B (V sub(1B) receptor) antagonists, TASP0233278 and TASP0390325. Experimental Approach We investigated the in vitro profiles of TASP0233278 and TASP0390325. In addition, the effect of TASP0390325 on the increase in plasma adrenocorticotropic hormone (ACTH) levels induced by corticotropin-releasing factor (CRF)/desmopressin (dDAVP) was investigated. We also investigated the antidepressant and anxiolytic profiles of TASP0233278 and TASP0390325 in animal models. Key Results Both TASP0233278 and TASP0390325 showed a high affinity and potent antagonist activity for V sub(1B) receptors. Oral administration of TASP0390325 antagonized the increase in plasma ACTH levels induced by CRF/dDAVP in rats, indicating that TASP0390325 blocks the anterior pituitary V sub(1B) receptor in vivo. Oral administration of TASP0233278 or TASP0390325 also exerted antidepressant effects in two models of depression (a forced swimming test and an olfactory bulbectomy model). Moreover, TASP0233278 improved depressive-like behaviour induced by repeated treatment with corticosterone, a model that has been shown to be resistant to treatment with currently prescribed antidepressants. In addition to depression models, TASP0233278 or TASP0390325 exerted anxiolytic effects in several anxiety models (social interaction, elevated plus-maze, stress-induced hyperthermia, separation-induced ultrasonic vocalization and sodium lactate-induced panic-like responses in panic-prone rats). Conclusion TASP0233278 and TASP0390325 are potent and orally active V sub(1B) receptor antagonists with antidepressant and anxiolytic activities in rodents.
Background and Purpose
Vasopressin V
1B
receptor antagonists may be effective for the treatment of depression and anxiety and the objective of this study was to characterize the pharmacological ...profiles of two newly synthesized arginine vasopressin receptor 1
B
(
V
1B
receptor) antagonists,
TASP
0233278 and
TASP
0390325.
Experimental Approach
We investigated the
in vitro
profiles of
TASP
0233278 and
TASP
0390325. In addition, the effect of
TASP
0390325 on the increase in plasma adrenocorticotropic hormone (
ACTH
) levels induced by corticotropin‐releasing factor (
CRF
)/desmopressin (d
DAVP
) was investigated. We also investigated the antidepressant and anxiolytic profiles of
TASP
0233278 and
TASP
0390325 in animal models.
Key Results
Both
TASP
0233278 and
TASP
0390325 showed a high affinity and potent antagonist activity for
V
1B
receptors. Oral administration of
TASP
0390325 antagonized the increase in plasma
ACTH
levels induced by
CRF
/d
DAVP
in rats, indicating that
TASP
0390325 blocks the anterior pituitary
V
1B
receptor
in vivo
. Oral administration of
TASP
0233278 or
TASP
0390325 also exerted antidepressant effects in two models of depression (a forced swimming test and an olfactory bulbectomy model). Moreover,
TASP
0233278 improved depressive‐like behaviour induced by repeated treatment with corticosterone, a model that has been shown to be resistant to treatment with currently prescribed antidepressants. In addition to depression models,
TASP
0233278 or
TASP
0390325 exerted anxiolytic effects in several anxiety models (social interaction, elevated plus‐maze, stress‐induced hyperthermia, separation‐induced ultrasonic vocalization and sodium lactate‐induced panic‐like responses in panic‐prone rats).
Conclusion
TASP
0233278 and
TASP
0390325 are potent and orally active
V
1B
receptor antagonists with antidepressant and anxiolytic activities in rodents.
In 1984, the authors first conducted a nationwide survey of deaf children with a history of maternal rubella (HMR) in special schools for the deaf in Japan. The survey showed that the incidence of ...congenital rubella syndrome in the Japanese mainlands was similar to those in the United States and Europe. In 1993, a second nationwide survey by the authors evaluated the efficacy of the vaccination program for schoolgirls begun in 1977. This second survey yielded 272 deaf children with HMR born between 1981 and 1989. Per 100,000 annual livebirths, the incidence rates were 1.56–9.95 in the epidemic years 1981–1982 and 1987–1988 and 0.20–0.72 in the interepidemic years. During the 1987–1988 epidemic, the incidence rates per 100,000 livebirths were 1.52 among mothers eligible for the vaccination program and 5.52–7.44 among mothers not eligible, and the difference was significant. However, only 21.7% of the women who delivered children during the 1987–1988 rubella epidemic were eligible for the vaccination program, and because the majority of deaf children with HMR were born to mothers not eligible, a decrease in the birth rate of deaf children with HMR was not observed. These data suggested the need to introduce a new vaccine program to suppress rubella epidemics. Am J Epidemiol 1998;148:263–8.
We investigated the agonistic activities of N4-{7-chloro-2-(E)-2-(2-chloro-phenyl)-vinyl-quinolin-4-yl}-N1,N1-diethyl-pentane-1,4-diamine (XIB4035), at the glial cell line-derived neurotrophic factor ...(GDNF) family receptorα-1(GFRα-1) in Neuro-2A cells, a mouse neuroblastoma cell line which is a suitable model for investigating functions mediated through GFRα-1. XIB4035 concentration-dependently inhibited 125IGDNF binding in Neuro-2A cells with an IC50 of 10.4μM. GDNF induced autophosphorylation of Ret protein, and promoted neurite outgrowth in Neuro-2A cells. XIB4035, like GDNF, induced Ret autophosphorylation in the Neuro-2A cells. Moreover, XIB4035 promoted neurite outgrowth in a concentration-dependent manner. These results show that XIB4035 may act as an agonist at GFRα-1 receptor complex, and mimic neurotrophic effects of GDNF in Neuro-2A cells. This is an interesting finding showing that a nonpeptidyl small molecule is capable of inducing activation of a receptor that normally bind a relatively large protein ligand such as GDNF.
Perinatal viral infections Ueda, K; Tokugawa, K; Kusuhara, K
Early human development,
06/1992, Letnik:
29, Številka:
1-3
Journal Article
Recenzirano
Among the TORCH agents, the occurrence of rubella and human T-lymphotropic virus type 1 (HTLV-1) in Japan were studied. Rubella epidemics occurred throughout Japan from 1964 to 1969 and from 1975 to ...1979. Low prevalences of CRS were observed in northeastern Japan, and high prevalences in southwestern Japan, with the highest in Okinawa. These conditions could be explained by the lower rate of rubella H1 antibody in the female population of southwestern Japan. Time of maternal rubella was in the gestational age interval from 26 to 57 days for cataract, from 25 to 62 days for heart disease and from 16 to 131 days for deafness. HTLV-1 is the causative agent of adult T-cell leukemia. Main route of transmission of this virus is mother-to-child transmission, through breast milk. Among the 311 mother-child pairs in Okinawa, 65 mothers (20.9%) and 10 children (3.2%) were seropositive for HTLV-1. Ten (15.4%) of the 65 seropositive mothers had seropositive children. These children had acquired their HTLV-1 antibodies by the age of 3 years. A significant difference existed between the prevalence rate of HTLV-1 antibodies in mothers and children.
In Japan, mass vaccination for diphtheria, pertussis, and/or tetanus has been mandated by the Vaccination Law since 1948. In order to evaluate the efficacy of this vaccination policy, we conducted ...seroepidemiological studies on pertussis, diphtheria, and tetanus among individuals aged 0 - 80 years. The pertussis toxin seropositive rates of the vaccine-eligible groups and vaccine-ineligible groups were 55.0 and 57.9%, respectively. The seropositive rate of each group for diphtheria antitoxin was 76.3 and 75.7%, respectively. The tetanus antitoxin seropositive rates were 91.7 and 10.5%, respectively, showing a significant difference between the two groups (P < 0.001). For the three diseases, variations were seen between age groups in the geometric mean antibody titers due to changes of the vaccination program. The results of this study show that natural Bordetella pertussis infection has occurred more frequently than expected. In order to establish the most appropriate vaccination program for the control of pertussis, diphtheria, and tetanus in Japan, further evaluation is necessary.
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