scholarly journals Anticonvulsant Action of a New Analogue of Allopregnanolone in Immature Rats

2010 ◽  
pp. 305-308
Author(s):  
P Mareš ◽  
H Kubová ◽  
A Kasal
Keyword(s):  
Clinical Trials ◽  
Acute Treatment ◽  
Age Groups ◽  
Neuroactive Steroid ◽  
Reference Drug ◽  
Anticonvulsant Action ◽  
Immature Rats ◽  
Effective Doses ◽  
Old Rats ◽  
Clonic Seizures

Neuroactive steroids represent potential antiepileptic drugs. We tested a newly synthesized analogue of allopregnanolone 3αhydroxy-21ξ,22-oxido-21-homo-5α-pregnan-20-on (HOHP) against two types of pentylenetetrazol-induced seizures (100 mg/kg s.c.) in 12- and 25-day-old rats. Ganaxolone, a neuroactive steroid in clinical trials, served as a reference drug. Pretreatment with either steroid suppressed generalized tonicclonic seizures in both age groups, their efficacy was comparable. HOHP as well as ganaxolone were more active in 12- than in 25-day-old rats (effective doses were 40 and 60 mg/kg, respectively). Minimal clonic seizures, which can be elicited only in 25-day-old rats, were not influenced by any drug. Very short duration of anticonvulsant action of HPOP demonstrated in 12-day-old animals indicates that this drug might be used only in acute treatment in epileptology.

scholarly journals Anticonvulsant action of GABA-B receptor agonist SKF97541 differs from that of Baclofen

2008 ◽  
pp. 789-792
Author(s):  
P Mareš
Keyword(s):  
Receptor Agonist ◽  
Age Groups ◽  
Mixed Effects ◽  
Adult Rats ◽  
Anticonvulsant Action ◽  
Generalized Seizures ◽  
Age Dependent ◽  
Old Rats ◽  
Clonic Seizures ◽  
Tonic Phase

GABA-B receptor agonist SKF97541 exhibits age-dependent anticonvulsant and proconvulsant actions in developing rats. It suppressed tonic phase of generalized seizures induced by pentetrazol in 7-, 12- and 18-day-old rats and increased their latency in 7- and 12-day-old animals. Other results in 18-day-old animals are not so clear. SKF97541 blocked the appearance of minimal clonic seizures, but tended to decrease latencies of both types of seizures. In addition, it significantly decreases latency of generalized seizures in adult rats. The mixed effects of SKF97541 are in agreement with those of baclofen but there are substantial differences between the actions of these two agonists in individual age groups.

scholarly journals AMN 082, an agonist of mGluR7, exhibits mixed anti- and proconvulsant effects in developing rats

2008 ◽  
pp. 969-972
Author(s):  
P Mareš
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Age Groups ◽  
Adult Rats ◽  
Anticonvulsant Action ◽  
Metabotropic Glutamate ◽  
Old Rats ◽  
Clonic Seizures ◽  
Motor Effects ◽  
Tonic Phase ◽  
Observation Period

Metabotropic glutamate receptors (mGluRs) represent a potential therapeutic target. Possible anticonvulsant action of AMN 082, an agonist of mGluR7 subtype, was studied in immature rats using pentylenetetrazol (PTZ)-induced seizures as a model. Five age groups of rats (7-, 12-, 18-, 25-day-old and adult animals) were pretreated with AMN 082 in doses of 0.5, 1, 2, and 5 mg/kg i.p. and 30 min later PTZ was administered (100 mg/kg s.c.). Controls received saline instead of the agonist. AMN 082 did not exhibit clear anticonvulsant action with the exception of suppression of the tonic phase of generalized tonic-clonic seizures (GTCS) in 12-day-old rats. Shorter latencies of GTCS after AMN 082 pretreatment indicate a proconvulsant action. Involuntary movements (mostly tremor) appeared after AMN 082 before PTZ administration, therefore we performed another experimental series with AMN 082 only (1, 2, 5, and 10 mg/kg i.p.). During 60-min observation period tremor appeared in all age groups; sensitivity to this action decreased with age from the 2 mg/kg dose in 7- and 12-day-old rats to the 10 mg/kg dose in adult rats. Mixed anti- and proconvulsant actions of AMN 082 together with unwanted motor effects makes clinical use of this drug highly improbable.

scholarly journals Anticonvulsant Action of GluN2A-Preferring Antagonist PEAQX in Developing Rats

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 415
Author(s):  
Pavel Mares ◽  
Grygoriy Tsenov ◽  
Hana Kubova
Keyword(s):  
Nmda Receptors ◽  
Postnatal Development ◽  
Age Groups ◽  
Developmental Differences ◽  
Dependent Manner ◽  
Anticonvulsant Action ◽  
Generalized Seizures ◽  
Lower Specificity ◽  
Old Rats ◽  
Convulsive Seizures

The GluN2A subunit of N-methyl-D-aspartate (NMDA) receptors becomes dominant during postnatal development, overgrowing the originally dominant GluN2B subunit. The aim of our study was to show changes of anticonvulsant action of the GluN2A subunit-preferring antagonist during postnatal development of rats. Possible anticonvulsant action of GluN2A-preferring antagonist of NMDA receptors P = [[[(1S)-1-(4-bromophenyl)ethyl]amino](1,2,3,4-tetrahydro-2,3-dioxo-5-quinoxalinyl)methyl]phosphonic acid tetrasodium salt (PEAQX) (5, 10, 20 mg/kg s.c.) was tested in 12-, 18-, and 25-day-old rats in three models of convulsive seizures. Pentylenetetrazol-induced generalized seizures with a loss of righting reflexes generated in the brainstem were suppressed in all three age groups in a dose-dependent manner. Minimal clonic seizures with preserved righting ability exhibited only moderately prolonged latency after the highest dose of PEAQX. Anticonvulsant action of all three doses of PEAQX against cortical epileptic afterdischarges (generated in the forebrain) was found in the 25-day-old animals. The highest dose (20 mg/kg) was efficient also in the two younger groups, which might be due to lower specificity of PEAQX and its partial affinity to the GluN2B subunit. Our results are in agreement with the postero-anterior maturation gradient of subunit composition of NMDA receptors (i.e., an increase of GluN2A representation). In spite of the lower selectivity of PEAQX, our data demonstrate, for the first time, developmental differences in comparison with an antagonist of NMDA receptors with a dominant GluN2B subunit.

scholarly journals Do Stereoisomers of Homocysteic Acid Exhibit Different Convulsant Action in Immature Rats?

2019 ◽  
pp. S361-S366
Author(s):  
P. MAREŠ ◽  
J. FOLBERGROVÁ ◽  
R. HAUGVICOVÁ ◽  
H. KUBOVÁ
Keyword(s):  
Nmda Receptors ◽  
Ampa Receptors ◽  
Dominant Role ◽  
Qualitative Difference ◽  
Homocysteic Acid ◽  
Immature Rats ◽  
Old Rats ◽  
Clonic Seizures

Mechanism of ictogenesis of D- and L-stereroisomers of homocysteic acid was studied in 12-day-old rats by means of antagonists of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. There was no qualitative difference between the two stereoisomers in generation of emprosthotonic (flexion) as well as generalized tonic-clonic seizures. Moderate differences were observed in the first, nonconvulsive effects of the two isomers. As generation of the two types of seizures is concerned, NMDA and AMPA participate in generalized tonic-clonic seizures whereas NMDA receptors play a dominant role in generation of flexion seizures.

Developmental changes in the tubular capacity for phosphate reabsorption in the rat

1988 ◽  
Vol 255 (2) ◽  
pp. F287-F291 ◽  
Author(s):  
A. Haramati ◽  
S. E. Mulroney ◽  
S. K. Webster
Keyword(s):  
Filtration Rate ◽  
Age Groups ◽  
The Other ◽  
Developmental Changes ◽  
Maximum Capacity ◽  
Phosphate Reabsorption ◽  
Immature Rats ◽  
Old Rats ◽  
Intrinsic Capacity ◽  
Filtered Load

The need for young, immature animals to maintain positive phosphate balance for growth is well known. However, whether this process involves changes in the intrinsic capacity of the kidney to reabsorb phosphate is not clear. In the present study, the maximum capacity of phosphate reabsorption [Max RPi/glomerular filtration rate (GFR)] was measured in four groups of rats at different stages of development, from weanling to adulthood (3–4, 5–6, 10–14, and 52 wk of age). Clearance experiments were performed in acutely thyroparathyroidectomized (TPTX) rats in the presence and absence of fixed levels of parathyroid hormone (synthetic PTH-(1–34), 1 U.kg-1.min-1). Max RPi/GFR was determined with progressive infusions of phosphate (0–6 mumol Pi/min) that raised the filtered load of phosphate. Max RPi/GFR in TPTX 3- to 4- and 5- to 6-wk-old rats (5.55 +/- 0.36 and 4.28 +/- 0.18 mumol/ml, respectively) was significantly greater than in the corresponding 52-wk-old rats (3.51 +/- 0.13 mumol/ml, P less than 0.05). PTH decreased the Max RPi/GFR in all age groups. However, the developmental pattern was maintained, with the highest levels present in the youngest rats (2.79 +/- 0.25 mumol/ml, P less than 0.05) compared with the other age groups (1.92 +/- 0.23, 1.35 +/- 0.11, and 1.15 +/- 0.13 mumol/ml for 5- to 6-, 10- to 14-, and 52-wk-old rats, respectively). These results demonstrate that the tubular capacity for phosphate reabsorption per milliliter GFR is enhanced in immature rats and progressively decreases with age. This PTH-independent adaptation in young rats may contribute to the renal retention of phosphate during growth.

Ethosuximide affects both pentylenetetrazole- and kainate-induced clonic seizures but differentiates between tonic–clonic seizures

1989 ◽  
Vol 67 (10) ◽  
pp. 1357-1361 ◽  
Author(s):  
Libor Velíšek ◽  
Ivana Kulhánková ◽  
Lenka Roztočilová ◽  
Pavel Mareš ◽  
Jana Velíšková ◽  
...  
Keyword(s):  
Age Groups ◽  
Similar Action ◽  
Young Rats ◽  
Wet Dog Shakes ◽  
Old Rats ◽  
Clonic Seizures

Young (25-day-old) and adult (90-day-old) rats pretreated with ethosuximide (62.5 or 125 mg/kg i.p.) were injected with either s.c. pentylenetetrazole (100 mg/kg) or i.p. kainate (10 or 14 mg/kg). The incidences and latencies of minor (clonic) and major (tonic–clonic) seizures were registered. Ethosuximide (125 mg/kg) completely blocked clonic seizures induced by the lower dose of kainate, and slightly suppressed or delayed those induced by the higher dose of kainate or pentylenetetrazole in both age groups. The effect of ethosuximide on major kainate-induced seizures (elicited in young rats only) was insignificant (ethosuximide only partially decreased the incidence of major seizures), whereas ethosuximide abolished major pentylenetetrazole-induced seizures in both age groups. Ethosuximide also failed to affect the latencies of kainate-induced automatisms (e.g., scratching, wet dog shakes). Similarities between kainate- and pentylenetetrazole-induced clonic seizures, as well as a similar action of ethosuximide on both, suggest a common generator for the pattern of clonic seizures.Key words: pentylenetetrazole, kainate, ethosuximide, seizures, rat.

EFFECT OF SERUM GONADOTROPHIN ON DEHYDROGENASES OF THE CITRIC ACID CYCLE IN THE OVARY OF THE RAT

1963 ◽  
Vol 42 (4) ◽  
pp. 480-484 ◽  
Author(s):  
B. Eckstein ◽  
R. Landsberg
Keyword(s):  
Citric Acid ◽  
Citric Acid Cycle ◽  
Age Groups ◽  
Succinic Dehydrogenase ◽  
Immature Rat ◽  
Acid Cycle ◽  
Immature Rats ◽  
Rat Ovary

ABSTRACT The succinic, malic and isocitric dehydrogenases in the ovary of immature and mature, normal and serum gonadotrophin injected rats were examined. The Qo2 of these enzymes were markedly enhanced in the gonadotrophin injected rats of both age groups, except in the case of succinic dehydrogenase in the ovary of the immature rats, where a slight non-significant decrease was noted. It is concluded that in the mature rat ovary, gonadotrophin administration stimulates the activity of all the examined dehydrogenases of the citric acid cycle, whereas in the immature rat ovary, at least the isocitric- and malic dehydrogenases are thus stimulated.

scholarly journals Barriers to Enrollment of Elderly Adults in Early-Phase Cancer Clinical Trials

2008 ◽  
Vol 4 (4) ◽  
pp. 162-168 ◽  
Author(s):  
Michele Basche ◽  
Anna E. Barón ◽  
S. Gail Eckhardt ◽  
Lodovico Balducci ◽  
Martha Persky ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Early Phase ◽  
Age Groups ◽  
Experimental Treatment ◽  
Cancer Center ◽  
Cancer Clinical Trials ◽  
Sources Of Information ◽  
Barriers To Participation ◽  
University Center ◽  
Barriers To Enrollment

Purpose: To describe patient/family and logistical barriers to participation in university-based, early-phase cancer clinical trials for adults age ≥ 65 years, and to identify influences on their decisions to participate. Participants and Methods: In-person surveys were administered to subjects age ≥ 65 years with advanced tumors who had received prior chemotherapy. Subjects were recruited from private medical oncology practices collaborating with the University of Colorado and Moffitt Cancer Center research networks. Results: Three hundred individuals (51% age 65 to 74 and 49% age 75 or older) responded. Overall, 60% reported one or more barriers to participation in an early-phase trial; logistical barriers such as driving or time demands (34%) or reluctance to be treated at a university center (21%) were most common. Seniors age 75 or older were more reluctant to be treated at a university center (27% v 14%; P = .005), or concerned about loss of continuity with their primary oncologist (24% v 15%, P = .05). Older seniors were also significantly more reluctant than younger seniors to consider treatments with substantial nausea, vomiting, or fatigue. Older and younger seniors differed little in their preferred sources of information; both age groups emphasized the importance of the primary oncologist (100%), a nurse who provides experimental treatment (93%), other patients (83%) or acquaintances who had received experimental treatment (83%). Conclusion: Potential strategies to overcome barriers to enrollment of seniors into early-phase trials include providing more information about trials to community oncologists and prospective enrollees and assisting these individuals in navigating logistical barriers to enrollment.

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