Chronic H1‐Antihistamine Treatment Increases Seizure Susceptibility After Withdrawal by Impairing Glutamine Synthetase

Abstract

Chronic H1-antihistamine treatment produces long-lasting increase in seizure susceptibility in nonepileptic rodents after drug withdrawal and its mechanism involves impairment of GS through blocking the action of histamine.

Gender difference in acquired seizure susceptibility in adult rats after early complex febrile seizures

“…The protocols for testing the threshold for MES in P11-P12 pups were modified from previous studies [20] . The threshold was determined using a rodent shocker (Hugo Sachs Elektronik, March-Hugstetten, Germany), which …”

Antipsychotic-Induced Dopamine Supersensitivity Psychosis: Pharmacology, Criteria, and Therapy

“…Pharmacological rebound is caused by a sudden increase or decrease in receptor-mediated effects due to removal of receptor blockade following drug discontinuation/dose reduction. This includes adrenergic rebound [99], cholinergic rebound [100,101], serotonin rebound [97], and histamine rebound [98]. We make a distinction between new and rebound symptoms, though they may have the same pharmacological mechanism [1,41,94].…”

“…In Tables 1 and 2, we integrate some of their findings on treatment-emergent symptoms related to removal of blockade or stimulation of dopamine and other receptors (serotonin, muscarinic, adrenergic, and histaminic receptors) by SGAs [94], and divide new antipsychotic-specific symptoms into: (1) serotonin withdrawal syndrome (equivalent to serotonin syndrome): flu-like symptoms, diarrhea, disorientation, coma, hyperreflexia, and stimulus-inducible clonus; (2) muscarinic withdrawal syndrome (also called cholinergic rebound syndrome): nausea, vomiting, abdominal cramps, hypothermia, increased salivation, tremor, parkinsonism, restlessness, and insomnia; (3) adrenergic withdrawal syndrome: increased blood pressure, headache, anxiety, agitation, increased heart rate, myocardial infarction, angina pectoris, palpitation, chest pain, presyncope, tremulousness, sweating, increased heart rate, myocardial infarction, hyperthermia, and fear; and (4) histaminic withdrawal syndrome: insomnia, agitation, tremulousness, increased seizure susceptibility, and amnesia (Table 2). Some new symptoms (Table 2) have been reported to occur more than 6 weeks after discontinuation: myocardial infarction and death after discontinuation of β-blockers [96]; hyperreflexia and inducible clonus after abrupt discontinuation of clozapine [97]; inducible seizure after discontinuation of chronic H 1 antihistamine treatment in rodents [98], and persistent insomnia following drug discontinuation/dose reduction of central muscarinic anticholinergics [1,90], and alcohol [95]. …”

Glutamine and Epilepsy

“…n = 7-9 ( a , b ); n = 7-11 ( c ). * P < 0.05, ** P < 0.01 Compared with control; ## P < 0.01 compared with saline-treated rats in control group; $ P < 0.05 compared with saline-treated rats in diphen group (Adapted from [ 46 ] and reproduced with permission from CNS Neurosci Ther\Blackwell Publishing Ltd)…”

“…In a study of the effect of chronic H1-antihistamine treatment on seizure susceptibility after drug withdrawal, it is found that chronic H1-antihistamines diphenhydramine and pyrilamine treatment produced long-lasting increase in seizure susceptibility together with the reduction of GS activity and glutamine and GABA level [ 46 ] (Fig. 31.5 ).…”