Dimetotiazine

Dimethothiazine (Dimetotiazine; Fonazine) is an orally active tricyclic anti-histamine, anti-5-HT agent with a high activity against decerebrate rigidity, a little sedative activity and little soporific action. Dimethothiazine can reduce or abolish the effects of both static and dynamic fusimotor activity on the muscle spindle in decerebrate cat. Dimethothiazine can be used to research hemicrania and spasticity[1][2][3].

Signaling Pathways >> Immunology/Inflammation >> Histamine Receptor

Research Areas >> Neurological Disease

Signaling Pathways >> GPCR/G Protein >> 5-HT Receptor

Signaling Pathways >> Neuronal Signaling >> 5-HT Receptor

Signaling Pathways >> GPCR/G Protein >> Histamine Receptor

Histamine, 5-HT[1]

Dimethothiazine (0.5-16 mg/kg; i.v.; single dosage) reduces decerebrate rigidity in cats[2]. Animal Model: Cats (decerebrate model; the carotid arteries were clamped and the mid-brain sectioned approximately between the colliculae)[2] Dosage: 0.5, 1, 2, 4, 8 and 16 mg/kg Administration: i.v.; single dosage Result: Reduced the discharge frequency of primary and secondary endings at 1-4 mg/kg. Reduced the sensitivity of the muscle spindle to stretch in preparations with intact ventral roots. Reduced the activity of the dynamic fusimotor fibres.

[1]. Nattero G, et al. Use of dimethothiazine in the prevention of hemicrania. Minerva Med. 1977 Mar 17;68(13):839-45.

[2]. Maxwell DR, Rhodes KF. The effects of dimethothiazine on muscle spindle activity in the decerebrate cat. Br J Pharmacol. 1970 Jul;39(3):520-32.

[3]. Griffiths MI, et al. The use of dimethothiazine in the treatment of childhood cerebral palsy. Dev Med Child Neurol. 1973 Feb;15(1):25-32.

MOLECULAR FORMULA :

C19-H25-N3-O2-S2

MOLECULAR WEIGHT :

391.59

WISWESSER LINE NOTATION :

T C666 BN ISJ B1Y1&N1&1 ESWN1&1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

740 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes

REFERENCE :

AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 159,70,1966

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

190 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes

REFERENCE :

AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 159,70,1966

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

475 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes

REFERENCE :

AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 159,70,1966

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

100 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes

REFERENCE :

AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 159,70,1966 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

600 mg/kg

SEX/DURATION :

female 9-14 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,381,1970