Antipsychotic-like profile of thioperamide, a selective H3-receptor antagonist in mice.
Experimental and clinical evidence points to a role of central histaminergic system in the pathogenesis of schizophrenia. The present study was designed to study the effect of histamine H(3)-receptor ligands on neuroleptic-induced catalepsy, apomorphine-induced climbing behavior and amphetamine-induced locomotor activities in mice. Catalepsy was induced by haloperidol (2 mg/kg p.o.), while apomorphine (1.5 mg/kg s.c.) and amphetamine (2 mg/kg s.c.) were used for studying climbing behavior and locomotor activities, respectively. (R)-alpha-methylhistamine (RAMH) (5 microg i.c.v.) and thioperamide (THP) (15 mg/kg i.p.), per se did not cause catalepsy. Administration of THP (3.75, 7.5 and 15 mg/kg i.p.) 1 h prior to haloperidol resulted in a dose-dependent increase in the catalepsy times (P < 0.05). However, pretreatment with RAMH significantly reversed such an effect of THP (15 mg/kg i.p.). RAMH per se showed significant reduction in locomotor time, distance traveled and average speed but THP (15 mg/kg i.p.) per se had no effect on these parameters. On amphetamine-induced hyperactivity, THP (3.75 and 7.5 mg/kg i.p.) reduced locomotor time, distance traveled and average speed (P < 0.05). Pretreatment with RAMH (5 microg i.c.v.) could partially reverse such effects of THP (3.75 mg/kg i.p.). Climbing behavior induced by apomorphine was reduced in animals treated with THP. Such an effect was, however, reversed in presence of RAMH. THP exhibited an antipsychotic-like profile by potentiating haloperidol-induced catalepsy, reducing amphetamine-induced hyperactivity and reducing apomorphine-induced climbing in mice. Such effects of THP were reversed by RAMH indicating the involvement of histamine H(3)-receptors. Findings suggest a potential for H(3)-receptor antagonists in improving the refractory cases of schizophrenia.
Akhtar
Mohd
M
Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, Hamdard University, New Delhi, India.
Uma Devi
P
P
Ali
Atif
A
Pillai
K K
KK
Vohora
Divya
D
D000661:Amphetamine; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001058:Apomorphine; D002375:Catalepsy / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D008761:Methylhistamines / Q000494:pharmacology; D051379:Mice; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D018100:Receptors, Histamine H3 / Q000187:drug effects* / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects; D013997:Time Factors
D014150:Antipsychotic Agents; D017442:Histamine Agonists; D006633:Histamine Antagonists; D008761:Methylhistamines; D010880:Piperidines; D018100:Receptors, Histamine H3; C069357:alpha-methylhistamine; D000661:Amphetamine; C052075:thioperamide; D006220:Haloperidol; D001058:Apomorphine